Bioinorganic Chemistry and Redox Homeostasis
Our website :
Metals in Biology and Redox Homeostasis
A new name for our research group: METROX
CONGRATULATIONS to our former PhD students:
Jean Bouvet for his selection to the MBA « collège des ingénieurs » (jan. 2024)
Paul Demay-Drouhard, who was appointed as a CNRS researcher (section 12, ICOA Orléans) in 2023
Martha Zoumpoulaki for her selection to the MBA « collège des ingénieurs » (oct. 2021) and her recruitment at Air Liquide in 2023.
Koudedja Coulibaly, who was recruited by Air Liquide in 2021
Emilie Mathieu, who was appointed as a CNRS researcher (section 16, LCC Toulouse) in 2021
Sarah Hostachy, who was appointed as a CEAEA researcher (LCBM, Grenoble) in 2020
Our personal webpages and resumes:
Alice Balfourier (ORCID: 0000-0002-4801-1388)
Hélène Bertrand (ORCID: 0000-0002-3841-022X)
Nicolas Delsuc (ORCID: 0000-0001-5570-8311)
Clotilde Policar (ORCID: 0000-0003-0255-1650)
Christine Rampon (ORCID: 0000-0002-1444-3166)
Michel Volovitch (ORCID: 0000-0002-7488-764X)
Sophie Vriz
Some news about our work:
About our work and equity in science (in French): https://www.youtube.com/watch?v=ZfyFIkh_G4k
https://www.inc.cnrs.fr/fr/cnrsinfo/des-complexes-bio-inspires-dans-le-vent
https://www.ens.psl.eu/actualites/des-catalyseurs-bio-inspires-pour-lutter-contre-le-stress-oxydant
Publications of the group:
((Go back to the publication page of the ens-bic website))
2017 |
Synthesis of Homoditopic Ligands with an Incrementable Rodlike Backbone Article de journal P Demay-Drouhard; L -M Chamoreau; R Guillot; C Policar; H C Bertrand European Journal of Organic Chemistry, 2017 (1), p. 131–137, 2017. @article{Demay-Drouhard:2017, title = {Synthesis of Homoditopic Ligands with an Incrementable Rodlike Backbone}, author = {P Demay-Drouhard and L -M Chamoreau and R Guillot and C Policar and H C Bertrand}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85007178925&doi=10.1002%2fejoc.201601081&partnerID=40&md5=4e3e60591df3842d6c169cf43161de0f}, doi = {10.1002/ejoc.201601081}, year = {2017}, date = {2017-01-01}, journal = {European Journal of Organic Chemistry}, volume = {2017}, number = {1}, pages = {131--137}, abstract = {We describe the synthesis of architectures that consist of a symmetrical rodlike oligo(phenylene-ethynylene) (OPE) backbone of incrementable length connected to a pair of classical ligands for metal coordination. OPE spacers decorated with various end groups and incorporating up to seven phenylene-acetylene repeat units were quickly obtained through a bidirectional approach. Efficient further functionalization with useful coordinating groups were achieved. The resulting homoditopic platforms are of interest in numerous fields ranging from supramolecular chemistry to materials science. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim}, keywords = {}, pubstate = {published}, tppubtype = {article} } We describe the synthesis of architectures that consist of a symmetrical rodlike oligo(phenylene-ethynylene) (OPE) backbone of incrementable length connected to a pair of classical ligands for metal coordination. OPE spacers decorated with various end groups and incorporating up to seven phenylene-acetylene repeat units were quickly obtained through a bidirectional approach. Efficient further functionalization with useful coordinating groups were achieved. The resulting homoditopic platforms are of interest in numerous fields ranging from supramolecular chemistry to materials science. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim |
Rhenium Complexes Based on 2-Pyridyl-1,2,3-triazole Ligands: A New Class of CO2 Reduction Catalysts Article de journal H Y V Ching; X Wang; M He; N Perujo Holland; R Guillot; C Slim; S Griveau; H C Bertrand; C Policar; F Bedioui; M Fontecave Inorganic Chemistry, 56 (5), p. 2966–2976, 2017. @article{Ching:2017, title = {Rhenium Complexes Based on 2-Pyridyl-1,2,3-triazole Ligands: A New Class of CO2 Reduction Catalysts}, author = {H Y V Ching and X Wang and M He and N Perujo Holland and R Guillot and C Slim and S Griveau and H C Bertrand and C Policar and F Bedioui and M Fontecave}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85014526293&doi=10.1021%2facs.inorgchem.6b03078&partnerID=40&md5=5aa6a6db21554e7bca56e0f1e1de9856}, doi = {10.1021/acs.inorgchem.6b03078}, year = {2017}, date = {2017-01-01}, journal = {Inorganic Chemistry}, volume = {56}, number = {5}, pages = {2966--2976}, abstract = {A series of [Re(NtextasciicircumN)(CO)3(X)] (NtextasciicircumN = diimine and X = halide) complexes based on 4-(2-pyridyl)-1,2,3-triazole (pyta) and 1-(2-pyridyl)-1,2,3-triazole (tapy) diimine ligands have been prepared and electrochemically characterized. The first ligand-based reduction process is shown to be highly sensitive to the nature of the isomer as well as to the substituents on the pyridyl ring, with the peak potential changing by up to 700 mV. The abilities of this class of complexes to catalyze the electroreduction and photoreduction of CO2 were assessed for the first time. It is found that only Re pyta complexes that have a first reduction wave with a peak potential at ca. −1.7 V vs SCE are active, producing CO as the major product, together with small amounts of H2 and formic acid. The catalytic wave that is observed in the CVs is enhanced by the addition of water or trifluoroethanol as a proton source. Long-term controlled potential electrolysis experiments gave total Faradaic yield close to 100%. In particular, functionalization of the triazolyl ring with a 2,4,6-tri-tert-butylphenyl group provided the catalyst with a remarkable stability. © 2017 American Chemical Society.}, keywords = {}, pubstate = {published}, tppubtype = {article} } A series of [Re(NtextasciicircumN)(CO)3(X)] (NtextasciicircumN = diimine and X = halide) complexes based on 4-(2-pyridyl)-1,2,3-triazole (pyta) and 1-(2-pyridyl)-1,2,3-triazole (tapy) diimine ligands have been prepared and electrochemically characterized. The first ligand-based reduction process is shown to be highly sensitive to the nature of the isomer as well as to the substituents on the pyridyl ring, with the peak potential changing by up to 700 mV. The abilities of this class of complexes to catalyze the electroreduction and photoreduction of CO2 were assessed for the first time. It is found that only Re pyta complexes that have a first reduction wave with a peak potential at ca. −1.7 V vs SCE are active, producing CO as the major product, together with small amounts of H2 and formic acid. The catalytic wave that is observed in the CVs is enhanced by the addition of water or trifluoroethanol as a proton source. Long-term controlled potential electrolysis experiments gave total Faradaic yield close to 100%. In particular, functionalization of the triazolyl ring with a 2,4,6-tri-tert-butylphenyl group provided the catalyst with a remarkable stability. © 2017 American Chemical Society. |
Re(I) carbonyl complexes: Multimodal platforms for inorganic chemical biology Article de journal S Hostachy; C Policar; N Delsuc Coordination Chemistry Reviews, 351 , p. 172–188, 2017. @article{Hostachy:2017, title = {Re(I) carbonyl complexes: Multimodal platforms for inorganic chemical biology}, author = {S Hostachy and C Policar and N Delsuc}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85020033654&doi=10.1016%2fj.ccr.2017.05.004&partnerID=40&md5=ea1241c6f9199448b3fbb2bfc259b363}, doi = {10.1016/j.ccr.2017.05.004}, year = {2017}, date = {2017-01-01}, journal = {Coordination Chemistry Reviews}, volume = {351}, pages = {172--188}, abstract = {Bio-imaging, by enabling the visualization of biomolecules of interest, has proved to be highly informative in the study of biological processes. Although fluorescence microscopy is probably one of the most used techniques, alternative methods of imaging, providing complementary information, are emerging. In this context, metal complexes represent valuable platforms for multimodal imaging, since they may combine interesting spectroscopic features and biologically relevant functionalization on a single molecular core. In particular, d6 low-spin rhenium tri-carbonyl complexes display unique luminescence and vibrational properties, and can be readily functionalized. Here we review their applications and potential as probes or drugs relying on their photophysical properties, before focusing on their use as multimodal probes for the labelling and imaging of peptides and proteins. © 2017 Elsevier B.V.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Bio-imaging, by enabling the visualization of biomolecules of interest, has proved to be highly informative in the study of biological processes. Although fluorescence microscopy is probably one of the most used techniques, alternative methods of imaging, providing complementary information, are emerging. In this context, metal complexes represent valuable platforms for multimodal imaging, since they may combine interesting spectroscopic features and biologically relevant functionalization on a single molecular core. In particular, d6 low-spin rhenium tri-carbonyl complexes display unique luminescence and vibrational properties, and can be readily functionalized. Here we review their applications and potential as probes or drugs relying on their photophysical properties, before focusing on their use as multimodal probes for the labelling and imaging of peptides and proteins. © 2017 Elsevier B.V. |
E Mathieu; A -S Bernard; N Delsuc; E Quévrain; G Gazzah; B Lai; F Chain; P Langella; M Bachelet; J Masliah; P Seksik; C Policar Inorganic Chemistry, 56 (5), p. 2545–2555, 2017. @article{Mathieu:2017, title = {A Cell-Penetrant Manganese Superoxide Dismutase (MnSOD) Mimic Is Able to Complement MnSOD and Exerts an Antiinflammatory Effect on Cellular and Animal Models of Inflammatory Bowel Diseases}, author = {E Mathieu and A -S Bernard and N Delsuc and E Qu\'{e}vrain and G Gazzah and B Lai and F Chain and P Langella and M Bachelet and J Masliah and P Seksik and C Policar}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85014763334&doi=10.1021%2facs.inorgchem.6b02695&partnerID=40&md5=acd51065ea36d5da707ec8c1915634a0}, doi = {10.1021/acs.inorgchem.6b02695}, year = {2017}, date = {2017-01-01}, journal = {Inorganic Chemistry}, volume = {56}, number = {5}, pages = {2545--2555}, abstract = {Inorganic complexes are increasingly used for biological and medicinal applications, and the question of the cell penetration and distribution of metallodrugs is key to understanding their biological activity. Oxidative stress is known to be involved in inflammation and in inflammatory bowel diseases for which antioxidative defenses are weakened. We report here the study of the manganese complex Mn1 mimicking superoxide dismutase (SOD), a protein involved in cell protection against oxidative stress, using an approach in inorganic cellular chemistry combining the investigation of Mn1 intracellular speciation using mass spectrometry and of its quantification and distribution using electron paramagnetic resonance and spatially resolved X-ray fluorescence with evaluation of its biological activity. More precisely, we have looked for and found the MS signature of Mn1 in cell lysates and quantified the overall manganese content. Intestinal epithelial cells activated by bacterial lipopolysaccharide were taken as a cellular model of oxidative stress and inflammation. DNBS-induced colitis in mice was used to investigate Mn1 activity in vivo. Mn1 exerts an intracellular antiinflammatory activity, remains at least partially coordinated, with diffuse distribution over the whole cell, and functionally complements mitochondrial MnSOD. © 2017 American Chemical Society.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Inorganic complexes are increasingly used for biological and medicinal applications, and the question of the cell penetration and distribution of metallodrugs is key to understanding their biological activity. Oxidative stress is known to be involved in inflammation and in inflammatory bowel diseases for which antioxidative defenses are weakened. We report here the study of the manganese complex Mn1 mimicking superoxide dismutase (SOD), a protein involved in cell protection against oxidative stress, using an approach in inorganic cellular chemistry combining the investigation of Mn1 intracellular speciation using mass spectrometry and of its quantification and distribution using electron paramagnetic resonance and spatially resolved X-ray fluorescence with evaluation of its biological activity. More precisely, we have looked for and found the MS signature of Mn1 in cell lysates and quantified the overall manganese content. Intestinal epithelial cells activated by bacterial lipopolysaccharide were taken as a cellular model of oxidative stress and inflammation. DNBS-induced colitis in mice was used to investigate Mn1 activity in vivo. Mn1 exerts an intracellular antiinflammatory activity, remains at least partially coordinated, with diffuse distribution over the whole cell, and functionally complements mitochondrial MnSOD. © 2017 American Chemical Society. |
Association of a Platinum Complex to a G-Quadruplex Ligand Enhances Telomere Disruption Article de journal R Charif; C Granotier-Beckers; H C Bertrand; J Poupon; E Ségal-Bendirdjian; M -P Teulade-Fichou; F D Boussin; S Bombard Chemical Research in Toxicology, 30 (8), p. 1629–1640, 2017. @article{Charif:2017, title = {Association of a Platinum Complex to a G-Quadruplex Ligand Enhances Telomere Disruption}, author = {R Charif and C Granotier-Beckers and H C Bertrand and J Poupon and E S\'{e}gal-Bendirdjian and M -P Teulade-Fichou and F D Boussin and S Bombard}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85027852578&doi=10.1021%2facs.chemrestox.7b00131&partnerID=40&md5=fd5e6afe1b7d7488cd33597bef254e71}, doi = {10.1021/acs.chemrestox.7b00131}, year = {2017}, date = {2017-01-01}, journal = {Chemical Research in Toxicology}, volume = {30}, number = {8}, pages = {1629--1640}, abstract = {Telomeres protect the ends of chromosomes against illegitimate recombination and repair. They can be targets for G-quadruplex ligands and platinum complexes due to their repeated G-rich sequences. Protection of telomeres is ensured by a complex of six proteins, including TRF2, which inhibits the DNA damage response pathway. We analyzed telomere modifications induced in cancer cells by the experimental hybrid platinum complex, Pt-MPQ, comprising both an ethylene diamine monofunctional platinum complex and a G-quadruplex recognition moiety (MPQ). Pt-MPQ promotes the displacement of two telomeric proteins (TRF2 and TRF1) from telomeres, as well as the formation of telomere damage and telomere sister losses, whereas the control compound MPQ does not. This suggests that the platinum moiety potentiates the targeting of the G-quadruplex ligand to telomeres, opening a new perspective for telomere biology and anticancer therapy. Interestingly, the chemotherapy drug cisplatin, which has no specific affinity for G-quadruplex structures, partially induces the TRF2 delocalization from telomeres but produces less telomeric DNA damage, suggesting that this TRF2 displacement could be independent of G-quadruplex recognition. © 2017 American Chemical Society.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Telomeres protect the ends of chromosomes against illegitimate recombination and repair. They can be targets for G-quadruplex ligands and platinum complexes due to their repeated G-rich sequences. Protection of telomeres is ensured by a complex of six proteins, including TRF2, which inhibits the DNA damage response pathway. We analyzed telomere modifications induced in cancer cells by the experimental hybrid platinum complex, Pt-MPQ, comprising both an ethylene diamine monofunctional platinum complex and a G-quadruplex recognition moiety (MPQ). Pt-MPQ promotes the displacement of two telomeric proteins (TRF2 and TRF1) from telomeres, as well as the formation of telomere damage and telomere sister losses, whereas the control compound MPQ does not. This suggests that the platinum moiety potentiates the targeting of the G-quadruplex ligand to telomeres, opening a new perspective for telomere biology and anticancer therapy. Interestingly, the chemotherapy drug cisplatin, which has no specific affinity for G-quadruplex structures, partially induces the TRF2 delocalization from telomeres but produces less telomeric DNA damage, suggesting that this TRF2 displacement could be independent of G-quadruplex recognition. © 2017 American Chemical Society. |
An All-in-One Molecule for the One-Step Synthesis of Functional Hybrid Silica Particles with Tunable Sizes Article de journal J Graffion; D Dems; M Demirelli; T Coradin; N Delsuc; C Aimé European Journal of Inorganic Chemistry, 2017 (43), p. 5047–5051, 2017. @article{Graffion:2017, title = {An All-in-One Molecule for the One-Step Synthesis of Functional Hybrid Silica Particles with Tunable Sizes}, author = {J Graffion and D Dems and M Demirelli and T Coradin and N Delsuc and C Aim\'{e}}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85035047611&doi=10.1002%2fejic.201701181&partnerID=40&md5=249333f958412776dc6966b033242102}, doi = {10.1002/ejic.201701181}, year = {2017}, date = {2017-01-01}, journal = {European Journal of Inorganic Chemistry}, volume = {2017}, number = {43}, pages = {5047--5051}, abstract = {Spherical particles with well-defined diameters were obtained by self-assembly of trityl-based molecules. Thanks to the robustness of the organic scaffold, a variety of modifications could be covalently introduced into the network so as to stabilize the supramolecular structure by a sol\textendashgel route. Using supramolecular chemistry, we showed that the synthesis of hybrid small molecules allowed engineering nanomaterials with tunable size and functionality. The use of a combination of different characterization techniques, including dynamic light scattering, cryoTEM, and solid-state NMR spectroscopy, provided careful understanding of the relationship between the molecular and supramolecular structures for further chemical engineering of supramolecular hybrid materials. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim}, keywords = {}, pubstate = {published}, tppubtype = {article} } Spherical particles with well-defined diameters were obtained by self-assembly of trityl-based molecules. Thanks to the robustness of the organic scaffold, a variety of modifications could be covalently introduced into the network so as to stabilize the supramolecular structure by a sol–gel route. Using supramolecular chemistry, we showed that the synthesis of hybrid small molecules allowed engineering nanomaterials with tunable size and functionality. The use of a combination of different characterization techniques, including dynamic light scattering, cryoTEM, and solid-state NMR spectroscopy, provided careful understanding of the relationship between the molecular and supramolecular structures for further chemical engineering of supramolecular hybrid materials. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim |
A host-guest system based on collagen-like triple-helix hybridization Article de journal N Delsuc; S Uchinomiya; A Ojida; I Hamachi Chemical Communications, 53 (51), p. 6856–6859, 2017. @article{Delsuc:2017, title = {A host-guest system based on collagen-like triple-helix hybridization}, author = {N Delsuc and S Uchinomiya and A Ojida and I Hamachi}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85021764142&doi=10.1039%2fc7cc03055j&partnerID=40&md5=702ef29356b9c2adcdde22eeaaafb981}, doi = {10.1039/c7cc03055j}, year = {2017}, date = {2017-01-01}, journal = {Chemical Communications}, volume = {53}, number = {51}, pages = {6856--6859}, abstract = {A strategy inspired by tweezer receptors has been employed to develop a new host-guest system. The hybridization into a collagen-like triple helix is the driving force for the recognition that occurs with high affinity and selectivity. Several systems have been screened to find the best host-guest pair and this strategy may be implemented for tag fused protein recognition. © 2017 The Royal Society of Chemistry.}, keywords = {}, pubstate = {published}, tppubtype = {article} } A strategy inspired by tweezer receptors has been employed to develop a new host-guest system. The hybridization into a collagen-like triple helix is the driving force for the recognition that occurs with high affinity and selectivity. Several systems have been screened to find the best host-guest pair and this strategy may be implemented for tag fused protein recognition. © 2017 The Royal Society of Chemistry. |
Erratum: Author Correction: Resonant out-of-phase fluorescence microscopy and remote imaging overcome spectral limitations (Nature communications (2017) 8 1 (969)) Article de journal J Quérard; R Zhang; Z Kelemen; M -A Plamont; X Xie; R Chouket; I Roemgens; Y Korepina; S Albright; E Ipendey; M Volovitch; H L Sladitschek; P Neveu; L Gissot; A Gautier; J -D Faure; V Croquette; T Le Saux; L Jullien Nature communications, 8 (1), p. 2173, 2017. @article{Querard:2017, title = {Erratum: Author Correction: Resonant out-of-phase fluorescence microscopy and remote imaging overcome spectral limitations (Nature communications (2017) 8 1 (969))}, author = {J Qu\'{e}rard and R Zhang and Z Kelemen and M -A Plamont and X Xie and R Chouket and I Roemgens and Y Korepina and S Albright and E Ipendey and M Volovitch and H L Sladitschek and P Neveu and L Gissot and A Gautier and J -D Faure and V Croquette and T Le Saux and L Jullien}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85058747083&doi=10.1038%2fs41467-017-02133-8&partnerID=40&md5=15b4153817b7bd74d9691a4083989504}, doi = {10.1038/s41467-017-02133-8}, year = {2017}, date = {2017-01-01}, journal = {Nature communications}, volume = {8}, number = {1}, pages = {2173}, abstract = {The Peer Review File associated with this Article was updated shortly after publication to redact from the authors' point-by-point response a description of unpublished work describing how Speed OPIOM may in future be used to facilitate discrimination between FRET and direct excitation.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The Peer Review File associated with this Article was updated shortly after publication to redact from the authors' point-by-point response a description of unpublished work describing how Speed OPIOM may in future be used to facilitate discrimination between FRET and direct excitation. |
Optical control of tumor induction in the Zebrafish Article de journal Z Feng; S Nam; F Hamouri; I Aujard; B Ducos; S Vriz; M Volovitch; L Jullien; S Lin; S Weiss; D Bensimon Scientific Reports, 7 (1), 2017. @article{Feng:2017, title = {Optical control of tumor induction in the Zebrafish}, author = {Z Feng and S Nam and F Hamouri and I Aujard and B Ducos and S Vriz and M Volovitch and L Jullien and S Lin and S Weiss and D Bensimon}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85028028076&doi=10.1038%2fs41598-017-09697-x&partnerID=40&md5=0590b4f2bc458a31e987356701b6c9f7}, doi = {10.1038/s41598-017-09697-x}, year = {2017}, date = {2017-01-01}, journal = {Scientific Reports}, volume = {7}, number = {1}, abstract = {The zebrafish has become an increasingly popular and valuable cancer model over the past few decades. While most zebrafish cancer models are generated by expressing mammalian oncogenes under tissue-specific promoters, here we describe a method that allows for the precise optical control of oncogene expression in live zebrafish. We utilize this technique to transiently or constitutively activate a typical human oncogene, kRASG12V, in zebrafish embryos and investigate the developmental and tumorigenic phenotypes. We demonstrate the spatiotemporal control of oncogene expression in live zebrafish, and characterize the different tumorigenic probabilities when kRASG12V is expressed transiently or constitutively at different developmental stages. Moreover, we show that light can be used to activate oncogene expression in selected tissues and single cells without tissue-specific promoters. Our work presents a novel approach to initiate and study cancer in zebrafish, and the high spatiotemporal resolution of this method makes it a valuable tool for studying cancer initiation from single cells. © 2017 The Author(s).}, keywords = {}, pubstate = {published}, tppubtype = {article} } The zebrafish has become an increasingly popular and valuable cancer model over the past few decades. While most zebrafish cancer models are generated by expressing mammalian oncogenes under tissue-specific promoters, here we describe a method that allows for the precise optical control of oncogene expression in live zebrafish. We utilize this technique to transiently or constitutively activate a typical human oncogene, kRASG12V, in zebrafish embryos and investigate the developmental and tumorigenic phenotypes. We demonstrate the spatiotemporal control of oncogene expression in live zebrafish, and characterize the different tumorigenic probabilities when kRASG12V is expressed transiently or constitutively at different developmental stages. Moreover, we show that light can be used to activate oncogene expression in selected tissues and single cells without tissue-specific promoters. Our work presents a novel approach to initiate and study cancer in zebrafish, and the high spatiotemporal resolution of this method makes it a valuable tool for studying cancer initiation from single cells. © 2017 The Author(s). |
Resonant out-of-phase fluorescence microscopy and remote imaging overcome spectral limitations Article de journal J Quérard; R Zhang; Z Kelemen; M -A Plamont; X Xie; R Chouket; I Roemgens; Y Korepina; S Albright; E Ipendey; M Volovitch; H L Sladitschek; P Neveu; L Gissot; A Gautier; J -D Faure; V Croquette; T Le Saux; L Jullien Nature Communications, 8 (1), 2017. @article{Querard:2017a, title = {Resonant out-of-phase fluorescence microscopy and remote imaging overcome spectral limitations}, author = {J Qu\'{e}rard and R Zhang and Z Kelemen and M -A Plamont and X Xie and R Chouket and I Roemgens and Y Korepina and S Albright and E Ipendey and M Volovitch and H L Sladitschek and P Neveu and L Gissot and A Gautier and J -D Faure and V Croquette and T Le Saux and L Jullien}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85031811446&doi=10.1038%2fs41467-017-00847-3&partnerID=40&md5=c320b3585a15085c192d20ee6faa36fa}, doi = {10.1038/s41467-017-00847-3}, year = {2017}, date = {2017-01-01}, journal = {Nature Communications}, volume = {8}, number = {1}, abstract = {We present speed out-of-phase imaging after optical modulation (OPIOM), which exploits reversible photoswitchable fluorophores as fluorescent labels and combines optimized periodic illumination with phase-sensitive detection to specifically retrieve the label signal. Speed OPIOM can extract the fluorescence emission from a targeted label in the presence of spectrally interfering fluorophores and autofluorescence. Up to four fluorescent proteins exhibiting a similar green fluorescence have been distinguished in cells either sequentially or in parallel. Speed OPIOM is compatible with imaging biological processes in real time in live cells. Finally speed OPIOM is not limited to microscopy but is relevant for remote imaging as well, in particular, under ambient light. Thus, speed OPIOM has proved to enable fast and quantitative live microscopic and remote-multiplexed fluorescence imaging of biological samples while filtering out noise, interfering fluorophores, as well as ambient light. © 2017 The Author(s).}, keywords = {}, pubstate = {published}, tppubtype = {article} } We present speed out-of-phase imaging after optical modulation (OPIOM), which exploits reversible photoswitchable fluorophores as fluorescent labels and combines optimized periodic illumination with phase-sensitive detection to specifically retrieve the label signal. Speed OPIOM can extract the fluorescence emission from a targeted label in the presence of spectrally interfering fluorophores and autofluorescence. Up to four fluorescent proteins exhibiting a similar green fluorescence have been distinguished in cells either sequentially or in parallel. Speed OPIOM is compatible with imaging biological processes in real time in live cells. Finally speed OPIOM is not limited to microscopy but is relevant for remote imaging as well, in particular, under ambient light. Thus, speed OPIOM has proved to enable fast and quantitative live microscopic and remote-multiplexed fluorescence imaging of biological samples while filtering out noise, interfering fluorophores, as well as ambient light. © 2017 The Author(s). |
Reversible Keap1 inhibitors are preferential pharmacological tools to modulate cellular mitophagy Article de journal Nikolaos D Georgakopoulos; Michele Frison; Maria Soledad Alvarez; Hélène Bertrand; Geoff Wells; Michelangelo Campanella Scientific Reports, 7 (1), p. 10303, 2017, ISSN: 2045-2322. @article{Georgakopoulos2017, title = {Reversible Keap1 inhibitors are preferential pharmacological tools to modulate cellular mitophagy}, author = {Nikolaos D Georgakopoulos and Michele Frison and Maria Soledad Alvarez and H\'{e}l{\`{e}}ne Bertrand and Geoff Wells and Michelangelo Campanella}, url = {https://doi.org/10.1038/s41598-017-07679-7}, doi = {10.1038/s41598-017-07679-7}, issn = {2045-2322}, year = {2017}, date = {2017-01-01}, journal = {Scientific Reports}, volume = {7}, number = {1}, pages = {10303}, abstract = {Mitophagy orchestrates the autophagic degradation of dysfunctional mitochondria preventing their pathological accumulation and contributing to cellular homeostasis. We previously identified a novel chemical tool (hereafter referred to as PMI), which drives mitochondria into autophagy without collapsing their membrane potential ($Delta$$Psi$m). PMI is an inhibitor of the protein-protein interaction (PPI) between the transcription factor Nrf2 and its negative regulator, Keap1 and is able to up-regulate the expression of autophagy-associated proteins, including p62/SQSTM1. Here we show that PMI promotes mitochondrial respiration, leading to a superoxide-dependent activation of mitophagy. Structurally distinct Keap1-Nrf2 PPI inhibitors promote mitochondrial turnover, while covalent Keap1 modifiers, including sulforaphane (SFN) and dimethyl fumarate (DMF), are unable to induce a similar response. Additionally, we demonstrate that SFN reverses the effects of PMI in co-treated cells by reducing the accumulation of p62 in mitochondria and subsequently limiting their autophagic degradation. This study highlights the unique features of Keap1-Nrf2 PPI inhibitors as inducers of mitophagy and their potential as pharmacological agents for the treatment of pathological conditions characterized by impaired mitochondrial quality control.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Mitophagy orchestrates the autophagic degradation of dysfunctional mitochondria preventing their pathological accumulation and contributing to cellular homeostasis. We previously identified a novel chemical tool (hereafter referred to as PMI), which drives mitochondria into autophagy without collapsing their membrane potential ($Delta$$Psi$m). PMI is an inhibitor of the protein-protein interaction (PPI) between the transcription factor Nrf2 and its negative regulator, Keap1 and is able to up-regulate the expression of autophagy-associated proteins, including p62/SQSTM1. Here we show that PMI promotes mitochondrial respiration, leading to a superoxide-dependent activation of mitophagy. Structurally distinct Keap1-Nrf2 PPI inhibitors promote mitochondrial turnover, while covalent Keap1 modifiers, including sulforaphane (SFN) and dimethyl fumarate (DMF), are unable to induce a similar response. Additionally, we demonstrate that SFN reverses the effects of PMI in co-treated cells by reducing the accumulation of p62 in mitochondria and subsequently limiting their autophagic degradation. This study highlights the unique features of Keap1-Nrf2 PPI inhibitors as inducers of mitophagy and their potential as pharmacological agents for the treatment of pathological conditions characterized by impaired mitochondrial quality control. |
2016 |
Indolin-2-one compounds targeting thioredoxin reductase as potential anticancer drug leads Article de journal Kamila K Kaminska; Helene C Bertrand; Hisashi Tajima; William C Stafford; Qing Cheng; Wan Chen; Geoffrey Wells; Elias S J Arner; Eng-Hui Chew Oncotarget, 7 (26), p. 40233–40251, 2016, ISSN: 1949-2553. @article{Kaminska2016, title = {Indolin-2-one compounds targeting thioredoxin reductase as potential anticancer drug leads}, author = {Kamila K Kaminska and Helene C Bertrand and Hisashi Tajima and William C Stafford and Qing Cheng and Wan Chen and Geoffrey Wells and Elias S J Arner and Eng-Hui Chew}, url = {https://www.ncbi.nlm.nih.gov/pubmed/27244886 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5130005/}, doi = {10.18632/oncotarget.9579}, issn = {1949-2553}, year = {2016}, date = {2016-05-01}, journal = {Oncotarget}, volume = {7}, number = {26}, pages = {40233--40251}, publisher = {Impact Journals LLC}, abstract = {Several compounds bearing the indolinone chemical scaffold are known to possess anticancer properties. For example, the tyrosine kinase inhibitor sunitinib is an arylideneindolin-2-one compound. The chemical versatility associated with structural modifications of indolinone compounds underlies the potential to discover additional derivatives possessing anticancer properties. Previously synthesized 3-(2-oxoethylidene)indolin-2-one compounds, also known as supercinnamaldehyde (SCA) compounds in reference to the parent compound 1 [1-methyl-3(2-oxopropylidene)indolin-2-one], bear a nitrogen-linked $alpha$,$beta$-unsaturated carbonyl (Michael acceptor) moiety. Here we found that analogs bearing N-substituents, in particular compound 4 and 5 carrying an N-butyl and N-benzyl substituent, respectively, were strongly cytotoxic towards human HCT 116 colorectal and MCF-7 breast carcinoma cells. These compounds also displayed strong thioredoxin reductase (TrxR) inhibitory activity that was likely attributed to the electrophilicity of the Michael acceptor moiety. Their selectivity towards cellular TrxR inhibition over related antioxidant enzymes glutathione reductase (GR), thioredoxin (Trx) and glutathione peroxidase (GPx) was mediated through targeting of the selenocysteine (Sec) residue in the highly accessible C-terminal active site of TrxR. TrxR inhibition mediated by indolin-2-one compounds led to cellular Trx oxidation, increased oxidative stress and activation of apoptosis signal-regulating kinase 1 (ASK1). These events also led to activation of p38 and JNK mitogen-activated protein kinase (MAPK) signaling pathways, and cell death with apoptotic features of PARP cleavage and caspase 3 activation. In conclusion, these results suggest that indolin-2-one-based compounds specifically targeting TrxR may serve as novel drug leads for anticancer therapy.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Several compounds bearing the indolinone chemical scaffold are known to possess anticancer properties. For example, the tyrosine kinase inhibitor sunitinib is an arylideneindolin-2-one compound. The chemical versatility associated with structural modifications of indolinone compounds underlies the potential to discover additional derivatives possessing anticancer properties. Previously synthesized 3-(2-oxoethylidene)indolin-2-one compounds, also known as supercinnamaldehyde (SCA) compounds in reference to the parent compound 1 [1-methyl-3(2-oxopropylidene)indolin-2-one], bear a nitrogen-linked $alpha$,$beta$-unsaturated carbonyl (Michael acceptor) moiety. Here we found that analogs bearing N-substituents, in particular compound 4 and 5 carrying an N-butyl and N-benzyl substituent, respectively, were strongly cytotoxic towards human HCT 116 colorectal and MCF-7 breast carcinoma cells. These compounds also displayed strong thioredoxin reductase (TrxR) inhibitory activity that was likely attributed to the electrophilicity of the Michael acceptor moiety. Their selectivity towards cellular TrxR inhibition over related antioxidant enzymes glutathione reductase (GR), thioredoxin (Trx) and glutathione peroxidase (GPx) was mediated through targeting of the selenocysteine (Sec) residue in the highly accessible C-terminal active site of TrxR. TrxR inhibition mediated by indolin-2-one compounds led to cellular Trx oxidation, increased oxidative stress and activation of apoptosis signal-regulating kinase 1 (ASK1). These events also led to activation of p38 and JNK mitogen-activated protein kinase (MAPK) signaling pathways, and cell death with apoptotic features of PARP cleavage and caspase 3 activation. In conclusion, these results suggest that indolin-2-one-based compounds specifically targeting TrxR may serve as novel drug leads for anticancer therapy. |
The Use of Mn(II) Bound to His-tags as Genetically Encodable Spin-Label for Nanometric Distance Determination in Proteins Article de journal H Y V Ching; F C Mascali; H C Bertrand; E M Bruch; P Demay-Drouhard; R M Rasia; C Policar; L C Tabares; S Un Journal of Physical Chemistry Letters, 7 (6), p. 1072–1076, 2016. @article{Ching:2016, title = {The Use of Mn(II) Bound to His-tags as Genetically Encodable Spin-Label for Nanometric Distance Determination in Proteins}, author = {H Y V Ching and F C Mascali and H C Bertrand and E M Bruch and P Demay-Drouhard and R M Rasia and C Policar and L C Tabares and S Un}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84962539336&doi=10.1021%2facs.jpclett.6b00362&partnerID=40&md5=16161dac85830ffcae821a41e6480d4c}, doi = {10.1021/acs.jpclett.6b00362}, year = {2016}, date = {2016-01-01}, journal = {Journal of Physical Chemistry Letters}, volume = {7}, number = {6}, pages = {1072--1076}, abstract = {A genetically encodable paramagnetic spin-label capable of self-assembly from naturally available components would offer a means for studying the in-cell structure and interactions of a protein by electron paramagnetic resonance (EPR). Here, we demonstrate pulse electron-electron double resonance (DEER) measurements on spin-labels consisting of Mn(II) ions coordinated to a sequence of histidines, so-called His-tags, that are ubiquitously added by genetic engineering to facilitate protein purification. Although the affinity of His-tags for Mn(II) was low (800 μM), Mn(II)-bound His-tags yielded readily detectable DEER time traces even at concentrations expected in cells. We were able to determine accurately the distance between two His-tag Mn(II) spin-labels at the ends of a rigid helical polyproline peptide of known structure, as well as at the ends of a completely cell-synthesized 3-helix bundle. This approach not only greatly simplifies the labeling procedure but also represents a first step towards using self-assembling metal spin-labels for in-cell distance measurements. © 2016 American Chemical Society.}, keywords = {}, pubstate = {published}, tppubtype = {article} } A genetically encodable paramagnetic spin-label capable of self-assembly from naturally available components would offer a means for studying the in-cell structure and interactions of a protein by electron paramagnetic resonance (EPR). Here, we demonstrate pulse electron-electron double resonance (DEER) measurements on spin-labels consisting of Mn(II) ions coordinated to a sequence of histidines, so-called His-tags, that are ubiquitously added by genetic engineering to facilitate protein purification. Although the affinity of His-tags for Mn(II) was low (800 μM), Mn(II)-bound His-tags yielded readily detectable DEER time traces even at concentrations expected in cells. We were able to determine accurately the distance between two His-tag Mn(II) spin-labels at the ends of a rigid helical polyproline peptide of known structure, as well as at the ends of a completely cell-synthesized 3-helix bundle. This approach not only greatly simplifies the labeling procedure but also represents a first step towards using self-assembling metal spin-labels for in-cell distance measurements. © 2016 American Chemical Society. |
RIDME spectroscopy on high-spin Mn2+ centers Article de journal D Akhmetzyanov; H Y V Ching; V Denysenkov; P Demay-Drouhard; H C Bertrand; L C Tabares; C Policar; T F Prisner; S Un Physical Chemistry Chemical Physics, 18 (44), p. 30857–30866, 2016. @article{Akhmetzyanov:2016, title = {RIDME spectroscopy on high-spin Mn2+ centers}, author = {D Akhmetzyanov and H Y V Ching and V Denysenkov and P Demay-Drouhard and H C Bertrand and L C Tabares and C Policar and T F Prisner and S Un}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85025823502&doi=10.1039%2fc6cp05239h&partnerID=40&md5=d3a6cd609c88b382cf0297ed361d4003}, doi = {10.1039/c6cp05239h}, year = {2016}, date = {2016-01-01}, journal = {Physical Chemistry Chemical Physics}, volume = {18}, number = {44}, pages = {30857--30866}, abstract = {Pulsed EPR dipolar spectroscopy is a powerful tool for determining the structure and conformational dynamics of biological macromolecules, as it allows precise measurements of distances in the range of 1.5-10 nm. Utilization of high-spin Mn2+ species as spin probes for distance measurements is of significant interest, because they are biologically compatible and endogenous in numerous biological systems. However, to date dipolar spectroscopy experiments with this kind of species have been underexplored. Here we present pulsed electron electron double resonance (PELDOR also called DEER) and relaxation-induced dipolar modulation enhancement (RIDME) experiments, which have been performed at W-band (94 GHz) and J-band frequencies (263 GHz) on a bis-MnDOTA (DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate) model system. The distances obtained from these experiments are in good agreement with predictions. RIDME experiments reveal a significantly higher modulation depth compared to PELDOR, which is an important consideration for biological samples. These experiments also feature higher harmonics of the dipolar coupling frequency due to effective multiple-quantum relaxation of high-spin Mn2+ as well as the multiple-component background function. Harmonics of the dipolar coupling frequency were taken into account by including additional terms in the kernel function of Tikhonov regularization analysis. © The Owner Societies 2016.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Pulsed EPR dipolar spectroscopy is a powerful tool for determining the structure and conformational dynamics of biological macromolecules, as it allows precise measurements of distances in the range of 1.5-10 nm. Utilization of high-spin Mn2+ species as spin probes for distance measurements is of significant interest, because they are biologically compatible and endogenous in numerous biological systems. However, to date dipolar spectroscopy experiments with this kind of species have been underexplored. Here we present pulsed electron electron double resonance (PELDOR also called DEER) and relaxation-induced dipolar modulation enhancement (RIDME) experiments, which have been performed at W-band (94 GHz) and J-band frequencies (263 GHz) on a bis-MnDOTA (DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate) model system. The distances obtained from these experiments are in good agreement with predictions. RIDME experiments reveal a significantly higher modulation depth compared to PELDOR, which is an important consideration for biological samples. These experiments also feature higher harmonics of the dipolar coupling frequency due to effective multiple-quantum relaxation of high-spin Mn2+ as well as the multiple-component background function. Harmonics of the dipolar coupling frequency were taken into account by including additional terms in the kernel function of Tikhonov regularization analysis. © The Owner Societies 2016. |
Photophysical properties of single core multimodal probe for imaging (SCoMPI) in a membrane model and in cells Article de journal S Hostachy; J -M Swiecicki; C Sandt; N Delsuc; C Policar Dalton Transactions, 45 (7), p. 2791–2795, 2016. @article{Hostachy:2016, title = {Photophysical properties of single core multimodal probe for imaging (SCoMPI) in a membrane model and in cells}, author = {S Hostachy and J -M Swiecicki and C Sandt and N Delsuc and C Policar}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84958064177&doi=10.1039%2fc5dt03819g&partnerID=40&md5=fb027086e6424b54b23cc2c11098e273}, doi = {10.1039/c5dt03819g}, year = {2016}, date = {2016-01-01}, journal = {Dalton Transactions}, volume = {45}, number = {7}, pages = {2791--2795}, abstract = {The spectroscopic properties of two luminescent Re(i) tricarbonyl complexes conjugated with two cell-penetrating peptides were examined. Fluorescence experiments and IR quantification in membrane models and in cells showed unexpectedly strong luminescence enhancement for one of the complexes in a lipid environment. © The Royal Society of Chemistry 2016.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The spectroscopic properties of two luminescent Re(i) tricarbonyl complexes conjugated with two cell-penetrating peptides were examined. Fluorescence experiments and IR quantification in membrane models and in cells showed unexpectedly strong luminescence enhancement for one of the complexes in a lipid environment. © The Royal Society of Chemistry 2016. |
New insight into the structural, electrochemical and biological aspects of macroacyclic Cu(II) complexes derived from S-substituted dithiocarbazate schiff bases Article de journal M L Low; L Maigre; M I M Tahir; E R T Tiekink; P Dorlet; R Guillot; T B Ravoof; R Rosli; J -M Pagès; C Policar; N Delsuc; K A Crouse European Journal of Medicinal Chemistry, 120 , p. 1–12, 2016. @article{Low:2016, title = {New insight into the structural, electrochemical and biological aspects of macroacyclic Cu(II) complexes derived from S-substituted dithiocarbazate schiff bases}, author = {M L Low and L Maigre and M I M Tahir and E R T Tiekink and P Dorlet and R Guillot and T B Ravoof and R Rosli and J -M Pag\`{e}s and C Policar and N Delsuc and K A Crouse}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84967102584&doi=10.1016%2fj.ejmech.2016.04.027&partnerID=40&md5=71cde180942655ac9c57205e82887fcf}, doi = {10.1016/j.ejmech.2016.04.027}, year = {2016}, date = {2016-01-01}, journal = {European Journal of Medicinal Chemistry}, volume = {120}, pages = {1--12}, abstract = {Copper (II) complexes synthesized from the products of condensation of S-methyl- and S-benzyldithiocarbazate with 2,5-hexanedione (SMHDH2 and SBHDH2 respectively) have been characterized using various physicochemical (elemental analysis, molar conductivity, magnetic susceptibility) and spectroscopic (infrared, electronic) methods. The structures of SMHDH2, its copper (II) complex, CuSMHD, and the related CuSBHD complex as well as a pyrrole byproduct, SBPY, have been determined by single crystal X-ray diffraction. In order to provide more insight into the behaviour of the complexes in solution, electron paramagnetic resonance (EPR) and electrochemical experiments were performed. Antibacterial activity and cytotoxicity were evaluated. The compounds, dissolved in 0.5% and 5% DMSO, showed a wide range of antibacterial activity against 10 strains of Gram-positive and Gram-negative bacteria. Investigations of the effects of efflux pumps and membrane penetration on antibacterial activity are reported herein. Antiproliferation activity was observed to be enhanced by complexation with copper. Preliminary screening showed Cu complexes are strongly active against human breast adenocarcinoma cancer cell lines MDA-MB-231 and MCF-7. © 2016 Published by Elsevier Masson SAS.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Copper (II) complexes synthesized from the products of condensation of S-methyl- and S-benzyldithiocarbazate with 2,5-hexanedione (SMHDH2 and SBHDH2 respectively) have been characterized using various physicochemical (elemental analysis, molar conductivity, magnetic susceptibility) and spectroscopic (infrared, electronic) methods. The structures of SMHDH2, its copper (II) complex, CuSMHD, and the related CuSBHD complex as well as a pyrrole byproduct, SBPY, have been determined by single crystal X-ray diffraction. In order to provide more insight into the behaviour of the complexes in solution, electron paramagnetic resonance (EPR) and electrochemical experiments were performed. Antibacterial activity and cytotoxicity were evaluated. The compounds, dissolved in 0.5% and 5% DMSO, showed a wide range of antibacterial activity against 10 strains of Gram-positive and Gram-negative bacteria. Investigations of the effects of efflux pumps and membrane penetration on antibacterial activity are reported herein. Antiproliferation activity was observed to be enhanced by complexation with copper. Preliminary screening showed Cu complexes are strongly active against human breast adenocarcinoma cancer cell lines MDA-MB-231 and MCF-7. © 2016 Published by Elsevier Masson SAS. |
Monitoring bicosomes containing antioxidants in normal and irradiated skin Article de journal E Fernández; S Hostachy; C Sandt; G Rodríguez; H C Bertrand; S Clède; M Cócera; A D L Maza; F Lambert; C Policar; O López RSC Advances, 6 (76), p. 72559–72567, 2016. @article{Fernandez:2016, title = {Monitoring bicosomes containing antioxidants in normal and irradiated skin}, author = {E Fern\'{a}ndez and S Hostachy and C Sandt and G Rodr\'{i}guez and H C Bertrand and S Cl\`{e}de and M C\'{o}cera and A D L Maza and F Lambert and C Policar and O L\'{o}pez}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84982684419&doi=10.1039%2fc6ra11170j&partnerID=40&md5=126bef944046a09450ae86ce5985c07f}, doi = {10.1039/c6ra11170j}, year = {2016}, date = {2016-01-01}, journal = {RSC Advances}, volume = {6}, number = {76}, pages = {72559--72567}, abstract = {This study evaluates the penetration of bicosome systems incorporating two different antioxidants into normal skin and skin exposed to ultraviolet-visible radiation (UV-VIS) by Fourier-transform infrared microspectroscopy (FT-IR) using synchrotron radiation. Bicosomes are phospholipid assemblies based on mixtures of discoidal lipid structures protected by spherical lipid vesicles able to incorporate different molecules. In the current work, the antioxidants incorporated in these systems were β-carotene and a Mn complex as a superoxide dismutase (SOD) mimic. Additionally, a rhenium tri-carbonyl derivative was incorporated in the bicosome systems in order to map their penetration following the tag specific carbonyl signal by FT-IR microspectroscopy. The characterization of bicosome systems using the dynamic light scattering technique (DLS) showed a modification in the size of the systems containing β-carotene (Bcβ) or MnII complex (BcMn). After skin permeation, FT-IR results indicated a higher and deeper penetration of the BcMn system than the Bcβ system into the skin. Likely, the different physicochemical properties of both antioxidants could be responsible for this effect. Moreover, the penetration of both bicosome systems in irradiated skin was lower in comparison with the normal skin. This fact could be a consequence of the alteration of water transport in the skin during the irradiation process. In conclusion, these results indicated the effectiveness of bicosome systems as skin carriers, and provide information to protect skin under radiation using antioxidants. © The Royal Society of Chemistry 2016.}, keywords = {}, pubstate = {published}, tppubtype = {article} } This study evaluates the penetration of bicosome systems incorporating two different antioxidants into normal skin and skin exposed to ultraviolet-visible radiation (UV-VIS) by Fourier-transform infrared microspectroscopy (FT-IR) using synchrotron radiation. Bicosomes are phospholipid assemblies based on mixtures of discoidal lipid structures protected by spherical lipid vesicles able to incorporate different molecules. In the current work, the antioxidants incorporated in these systems were β-carotene and a Mn complex as a superoxide dismutase (SOD) mimic. Additionally, a rhenium tri-carbonyl derivative was incorporated in the bicosome systems in order to map their penetration following the tag specific carbonyl signal by FT-IR microspectroscopy. The characterization of bicosome systems using the dynamic light scattering technique (DLS) showed a modification in the size of the systems containing β-carotene (Bcβ) or MnII complex (BcMn). After skin permeation, FT-IR results indicated a higher and deeper penetration of the BcMn system than the Bcβ system into the skin. Likely, the different physicochemical properties of both antioxidants could be responsible for this effect. Moreover, the penetration of both bicosome systems in irradiated skin was lower in comparison with the normal skin. This fact could be a consequence of the alteration of water transport in the skin during the irradiation process. In conclusion, these results indicated the effectiveness of bicosome systems as skin carriers, and provide information to protect skin under radiation using antioxidants. © The Royal Society of Chemistry 2016. |
Human TTR conformation altered by rhenium tris-carbonyl derivatives Article de journal L Ciccone; C Policar; E A Stura; W Shepard Journal of Structural Biology, 195 (3), p. 353–364, 2016. @article{Ciccone:2016, title = {Human TTR conformation altered by rhenium tris-carbonyl derivatives}, author = {L Ciccone and C Policar and E A Stura and W Shepard}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84991363542&doi=10.1016%2fj.jsb.2016.07.002&partnerID=40&md5=86e7e8d956bfdb39ae832e52b01a9dea}, doi = {10.1016/j.jsb.2016.07.002}, year = {2016}, date = {2016-01-01}, journal = {Journal of Structural Biology}, volume = {195}, number = {3}, pages = {353--364}, abstract = {Transthyretin (TTR) is a 54 kDa homotetrameric serum protein that transports thyroxine (T4) and retinol. TTR is potentially amyloidogenic due to homotetramer dissociation into monomeric intermediates that self-assemble as amyloid deposits and insoluble fibrils. Most crystallographic structures, including those of amyloidogenic variants show the same tetramer without major variations in the monomer-monomer interface nor in the volume of the interdimeric cavity. Soaking TTR crystals in a solution containing rhenium tris-carbonyl derivatives yields a TTR conformer never observed before. Only one of the two monomers of the crystallographic dimer is significantly altered, and the inner part of the T4 binding cavity is expanded at one end and shrunk at the other. The result redefines the mechanism of allosteric communication between the two sites, suggesting that negative cooperativity is a function of dimer asymmetry, which can be induced through internal or external binding. An aspect that remains unexplained is why the conformational changes are ubiquitous throughout the crystal although the heavy metal content of the derivatized crystals is relatively low. The conformational changes observed, which include Leu82, may represent a form of TTR better at scavenging β-Amyloid. At a resolution of 1.69 r{A}, with excellent refinement statistics and well defined electron density for all parts of the structure, it is possible to envisage answering important questions that range from protein cooperative behavior to heavy atom induced protein conformational modifications that can result in crystallographic non-isomorphism. © 2016 Elsevier Inc.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Transthyretin (TTR) is a 54 kDa homotetrameric serum protein that transports thyroxine (T4) and retinol. TTR is potentially amyloidogenic due to homotetramer dissociation into monomeric intermediates that self-assemble as amyloid deposits and insoluble fibrils. Most crystallographic structures, including those of amyloidogenic variants show the same tetramer without major variations in the monomer-monomer interface nor in the volume of the interdimeric cavity. Soaking TTR crystals in a solution containing rhenium tris-carbonyl derivatives yields a TTR conformer never observed before. Only one of the two monomers of the crystallographic dimer is significantly altered, and the inner part of the T4 binding cavity is expanded at one end and shrunk at the other. The result redefines the mechanism of allosteric communication between the two sites, suggesting that negative cooperativity is a function of dimer asymmetry, which can be induced through internal or external binding. An aspect that remains unexplained is why the conformational changes are ubiquitous throughout the crystal although the heavy metal content of the derivatized crystals is relatively low. The conformational changes observed, which include Leu82, may represent a form of TTR better at scavenging β-Amyloid. At a resolution of 1.69 Å, with excellent refinement statistics and well defined electron density for all parts of the structure, it is possible to envisage answering important questions that range from protein cooperative behavior to heavy atom induced protein conformational modifications that can result in crystallographic non-isomorphism. © 2016 Elsevier Inc. |
Bioinspired superoxide-dismutase mimics: The effects of functionalization with cationic polyarginine peptides Article de journal H Y V Ching; I Kenkel; N Delsuc; E Mathieu; I Ivanović-Burmazović; C Policar Journal of Inorganic Biochemistry, 160 , p. 172–179, 2016. @article{Ching:2016a, title = {Bioinspired superoxide-dismutase mimics: The effects of functionalization with cationic polyarginine peptides}, author = {H Y V Ching and I Kenkel and N Delsuc and E Mathieu and I Ivanovi\'{c}-Burmazovi\'{c} and C Policar}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84964372716&doi=10.1016%2fj.jinorgbio.2016.01.025&partnerID=40&md5=035d0c2b5ffd4ee0b6fb74df285838da}, doi = {10.1016/j.jinorgbio.2016.01.025}, year = {2016}, date = {2016-01-01}, journal = {Journal of Inorganic Biochemistry}, volume = {160}, pages = {172--179}, abstract = {Continuing a bio-mimetic approach, we have prepared peptide conjugates of a superoxide dismutase (SOD) mimic [MnL]+ (where HL = N-(2-hydroxybenzyl)-N,N'-bis[2-(N-methylimidazolyl)methyl]ethane-1,2-diamine), namely [MnL'-Arg(n-1)]n+ (where n = 2, 4, 7 and 10) and [MnL'-Gly1]+. [MnL'-Arg(n-1)]n+ contained cationic residue(s) that emulate the electrostatic channel of the enzyme. Physicochemical methods showed that functionalization at the secondary amine of HL did not impair coordination to MnII with association constants (Kassoc) between 1.6 and 3.3 × 106 M- 1. The MnIII/MnII redox potential of the conjugates was between 0.27 and 0.30 V vs SCE, slightly higher than [MnL]+ under the same conditions, but remain at a value that facilitates O2•- dismutation. The catalytic rate constant (kcat) of the dismutation for the series was studied using a direct stopped-flow method, which showed that for compounds with the same overall charge, the alkylation of the secondary amine of [MnL]+ (kcat = 5.0 ± 0.1 × 106 M- 1 s- 1) led to a lower value (i.e. for [MnL'Gly]+}, keywords = {}, pubstate = {published}, tppubtype = {article} } Continuing a bio-mimetic approach, we have prepared peptide conjugates of a superoxide dismutase (SOD) mimic [MnL]+ (where HL = N-(2-hydroxybenzyl)-N,N'-bis[2-(N-methylimidazolyl)methyl]ethane-1,2-diamine), namely [MnL'-Arg(n-1)]n+ (where n = 2, 4, 7 and 10) and [MnL'-Gly1]+. [MnL'-Arg(n-1)]n+ contained cationic residue(s) that emulate the electrostatic channel of the enzyme. Physicochemical methods showed that functionalization at the secondary amine of HL did not impair coordination to MnII with association constants (Kassoc) between 1.6 and 3.3 × 106 M- 1. The MnIII/MnII redox potential of the conjugates was between 0.27 and 0.30 V vs SCE, slightly higher than [MnL]+ under the same conditions, but remain at a value that facilitates O2•- dismutation. The catalytic rate constant (kcat) of the dismutation for the series was studied using a direct stopped-flow method, which showed that for compounds with the same overall charge, the alkylation of the secondary amine of [MnL]+ (kcat = 5.0 ± 0.1 × 106 M- 1 s- 1) led to a lower value (i.e. for [MnL'Gly]+ |
Bimodal X-ray and Infrared Imaging of an Organometallic Derivative of Praziquantel in Schistosoma mansoni Article de journal S Clède; N Cowan; F Lambert; H C Bertrand; R Rubbiani; M Patra; J Hess; C Sandt; N Trcera; G Gasser; J Keiser; C Policar ChemBioChem, 17 (11), p. 1004–1007, 2016. @article{Clede:2016, title = {Bimodal X-ray and Infrared Imaging of an Organometallic Derivative of Praziquantel in Schistosoma mansoni}, author = {S Cl\`{e}de and N Cowan and F Lambert and H C Bertrand and R Rubbiani and M Patra and J Hess and C Sandt and N Trcera and G Gasser and J Keiser and C Policar}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84973124415&doi=10.1002%2fcbic.201500688&partnerID=40&md5=608b1bb28a5237e0717a29ee815e73bc}, doi = {10.1002/cbic.201500688}, year = {2016}, date = {2016-01-01}, journal = {ChemBioChem}, volume = {17}, number = {11}, pages = {1004--1007}, abstract = {An organometallic derivative of praziquantel was studied directly in worms by using inductively coupled plasma-mass spectrometry (ICP-MS) for quantification and synchrotron-based imaging. X-ray fluorescence (XRF) and IR absorption spectromicroscopy were used for the first time in combination to directly locate this organometallic drug candidate in schistosomes. The detection of both CO (IR) and Cr (XRF) signatures proved that the Cr(CO)3 core remained intact in the worms. Images showed a preferential accumulation at the worm's tegument, consistent with a possible targeting of the calcium channel but not excluding other biological targets inside the worm. Imaginative imaging: Two synchrotron-based techniques - X-ray fluorescence and IR absorption spectroscopy - were used in combination for the first time to directly locate an organometallic drug candidate in schistosomes. This represents a novel approach to examine mechanisms of actions for organometallic compounds and might lead to the discovery of new drug candidates. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.}, keywords = {}, pubstate = {published}, tppubtype = {article} } An organometallic derivative of praziquantel was studied directly in worms by using inductively coupled plasma-mass spectrometry (ICP-MS) for quantification and synchrotron-based imaging. X-ray fluorescence (XRF) and IR absorption spectromicroscopy were used for the first time in combination to directly locate this organometallic drug candidate in schistosomes. The detection of both CO (IR) and Cr (XRF) signatures proved that the Cr(CO)3 core remained intact in the worms. Images showed a preferential accumulation at the worm's tegument, consistent with a possible targeting of the calcium channel but not excluding other biological targets inside the worm. Imaginative imaging: Two synchrotron-based techniques - X-ray fluorescence and IR absorption spectroscopy - were used in combination for the first time to directly locate an organometallic drug candidate in schistosomes. This represents a novel approach to examine mechanisms of actions for organometallic compounds and might lead to the discovery of new drug candidates. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
A Bis-Manganese(II)–DOTA Complex for Pulsed Dipolar Spectroscopy Article de journal P Demay-Drouhard; H Y V Ching; D Akhmetzyanov; R Guillot; L C Tabares; H C Bertrand; C Policar ChemPhysChem, p. 2066–2078, 2016. @article{Demay-Drouhard:2016, title = {A Bis-Manganese(II)\textendashDOTA Complex for Pulsed Dipolar Spectroscopy}, author = {P Demay-Drouhard and H Y V Ching and D Akhmetzyanov and R Guillot and L C Tabares and H C Bertrand and C Policar}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84977597209&doi=10.1002%2fcphc.201600234&partnerID=40&md5=38a2466ad0f00d0edb158d200429986c}, doi = {10.1002/cphc.201600234}, year = {2016}, date = {2016-01-01}, journal = {ChemPhysChem}, pages = {2066--2078}, abstract = {High-spin gadolinium(III) and manganese(II) complexes have emerged as alternatives to standard nitroxide radical spin labels for measuring nanometric distances by using pulsed electron\textendashelectron double resonance (PELDOR or DEER) at high fields/frequencies. For certain complexes, particularly those with relatively small zero-field splitting (ZFS) and short distances between the two metal centers, the pseudosecular term of the dipolar coupling Hamiltonian is non-negligible. However, in general, the contribution from this term during conventional data analysis is masked by the flexibility of the molecule of interest and/or the long tethers connecting them to the spin labels. The efficient synthesis of a model system consisting of two [Mn(dota)]2− (MnDOTA; DOTA4−=1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate) directly connected to the ends of a central rodlike oligo(phenylene\textendashethynylene) (OPE) spacer is reported. The rigidity of the OPE is confirmed by Q-band PELDOR measurements on a bis-nitroxide analogue. The MnII−MnII distance distribution profile determined by W-band PELDOR is in reasonable agreement with one simulated by using a simple rotamer analysis. The small degree of flexibility arising from the linking MnDOTA arm appears to outweigh the contribution from the pseudosecular term at this interspin distance. This study illustrates the potential of MnDOTA-based spin labels for measuring fairly short nanometer distances, and also presents an interesting candidate for in-depth studies of pulsed dipolar spectroscopy methods on MnII−MnII systems. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim}, keywords = {}, pubstate = {published}, tppubtype = {article} } High-spin gadolinium(III) and manganese(II) complexes have emerged as alternatives to standard nitroxide radical spin labels for measuring nanometric distances by using pulsed electron–electron double resonance (PELDOR or DEER) at high fields/frequencies. For certain complexes, particularly those with relatively small zero-field splitting (ZFS) and short distances between the two metal centers, the pseudosecular term of the dipolar coupling Hamiltonian is non-negligible. However, in general, the contribution from this term during conventional data analysis is masked by the flexibility of the molecule of interest and/or the long tethers connecting them to the spin labels. The efficient synthesis of a model system consisting of two [Mn(dota)]2− (MnDOTA; DOTA4−=1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate) directly connected to the ends of a central rodlike oligo(phenylene–ethynylene) (OPE) spacer is reported. The rigidity of the OPE is confirmed by Q-band PELDOR measurements on a bis-nitroxide analogue. The MnII−MnII distance distribution profile determined by W-band PELDOR is in reasonable agreement with one simulated by using a simple rotamer analysis. The small degree of flexibility arising from the linking MnDOTA arm appears to outweigh the contribution from the pseudosecular term at this interspin distance. This study illustrates the potential of MnDOTA-based spin labels for measuring fairly short nanometer distances, and also presents an interesting candidate for in-depth studies of pulsed dipolar spectroscopy methods on MnII−MnII systems. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim |
Indolin-2-one compounds targeting thioredoxin reductase as potential anticancer drug leads Article de journal K K Kaminska; H C Bertrand; H Tajima; W C Stafford; Q Cheng; W Chen; G Wells; E S J Arner; E -H Chew Oncotarget, 7 (26), p. 40233–40251, 2016. @article{Kaminska:2016, title = {Indolin-2-one compounds targeting thioredoxin reductase as potential anticancer drug leads}, author = {K K Kaminska and H C Bertrand and H Tajima and W C Stafford and Q Cheng and W Chen and G Wells and E S J Arner and E -H Chew}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84983002228&doi=10.18632%2foncotarget.9579&partnerID=40&md5=21b5120cc53147d2dce47cf9545ab207}, doi = {10.18632/oncotarget.9579}, year = {2016}, date = {2016-01-01}, journal = {Oncotarget}, volume = {7}, number = {26}, pages = {40233--40251}, abstract = {Several compounds bearing the indolinone chemical scaffold are known to possess anticancer properties. For example, the tyrosine kinase inhibitor sunitinib is an arylideneindolin-2-one compound. The chemical versatility associated with structural modifications of indolinone compounds underlies the potential to discover additional derivatives possessing anticancer properties. Previously synthesized 3-(2-oxoethylidene)indolin-2-one compounds, also known as supercinnamaldehyde (SCA) compounds in reference to the parent compound 1 [1-methyl-3(2- oxopropylidene)indolin-2-one], bear a nitrogen-linked α,β-unsaturated carbonyl (Michael acceptor) moiety. Here we found that analogs bearing N-substituents, in particular compound 4 and 5 carrying an N-butyl and N-benzyl substituent, respectively, were strongly cytotoxic towards human HCT 116 colorectal and MCF-7 breast carcinoma cells. These compounds also displayed strong thioredoxin reductase (TrxR) inhibitory activity that was likely attributed to the electrophilicity of the Michael acceptor moiety. Their selectivity towards cellular TrxR inhibition over related antioxidant enzymes glutathione reductase (GR), thioredoxin (Trx) and glutathione peroxidase (GPx) was mediated through targeting of the selenocysteine (Sec) residue in the highly accessible C-terminal active site of TrxR. TrxR inhibition mediated by indolin-2-one compounds led to cellular Trx oxidation, increased oxidative stress and activation of apoptosis signal-regulating kinase 1 (ASK1). These events also led to activation of p38 and JNK mitogen-activated protein kinase (MAPK) signaling pathways, and cell death with apoptotic features of PARP cleavage and caspase 3 activation. In conclusion, these results suggest that indolin-2-one-based compounds specifically targeting TrxR may serve as novel drug leads for anticancer therapy.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Several compounds bearing the indolinone chemical scaffold are known to possess anticancer properties. For example, the tyrosine kinase inhibitor sunitinib is an arylideneindolin-2-one compound. The chemical versatility associated with structural modifications of indolinone compounds underlies the potential to discover additional derivatives possessing anticancer properties. Previously synthesized 3-(2-oxoethylidene)indolin-2-one compounds, also known as supercinnamaldehyde (SCA) compounds in reference to the parent compound 1 [1-methyl-3(2- oxopropylidene)indolin-2-one], bear a nitrogen-linked α,β-unsaturated carbonyl (Michael acceptor) moiety. Here we found that analogs bearing N-substituents, in particular compound 4 and 5 carrying an N-butyl and N-benzyl substituent, respectively, were strongly cytotoxic towards human HCT 116 colorectal and MCF-7 breast carcinoma cells. These compounds also displayed strong thioredoxin reductase (TrxR) inhibitory activity that was likely attributed to the electrophilicity of the Michael acceptor moiety. Their selectivity towards cellular TrxR inhibition over related antioxidant enzymes glutathione reductase (GR), thioredoxin (Trx) and glutathione peroxidase (GPx) was mediated through targeting of the selenocysteine (Sec) residue in the highly accessible C-terminal active site of TrxR. TrxR inhibition mediated by indolin-2-one compounds led to cellular Trx oxidation, increased oxidative stress and activation of apoptosis signal-regulating kinase 1 (ASK1). These events also led to activation of p38 and JNK mitogen-activated protein kinase (MAPK) signaling pathways, and cell death with apoptotic features of PARP cleavage and caspase 3 activation. In conclusion, these results suggest that indolin-2-one-based compounds specifically targeting TrxR may serve as novel drug leads for anticancer therapy. |
Small Fluorescence-Activating and Absorption-Shifting Tag for Tunable Protein Imaging in Vivo Article de journal Marie-Aude Plamont; Emmanuelle Billon-Denis; Sylvie Maurin; Carole Gauron; Frederico M Pimenta; Christian G Specht; Jian Shi; Jérôme Querard; Buyan Pan; Julien Rossignol; Karine Moncoq; Nelly Morellet; Michel Volovitch; Ewen Lescop; Yong Chen; Antoine Triller; Sophie Vriz; Thomas Le Saux; Ludovic Jullien; Arnaud Gautier Proceedings of the National Academy of Sciences, 113 (3), p. 497, 2016. @article{RN50, title = {Small Fluorescence-Activating and Absorption-Shifting Tag for Tunable Protein Imaging in Vivo}, author = {Marie-Aude Plamont and Emmanuelle {Billon-Denis} and Sylvie Maurin and Carole Gauron and Frederico M Pimenta and Christian G Specht and Jian Shi and J\'{e}r\^{o}me Querard and Buyan Pan and Julien Rossignol and Karine Moncoq and Nelly Morellet and Michel Volovitch and Ewen Lescop and Yong Chen and Antoine Triller and Sophie Vriz and Thomas Le Saux and Ludovic Jullien and Arnaud Gautier}, doi = {10.1073/pnas.1513094113}, year = {2016}, date = {2016-01-01}, journal = {Proceedings of the National Academy of Sciences}, volume = {113}, number = {3}, pages = {497}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
2015 |
Structure-based design of novel naproxen derivatives targeting monomeric nucleoprotein of Influenza A virus Article de journal Bogdan Tarus; Hélène Bertrand; Gloria Zedda; Carmelo Di Primo; Stéphane Quideau; Anny Slama-Schwok Journal of biomolecular structure & dynamics, 33 (9), p. 1899–1912, 2015, ISSN: 1538-0254. @article{Tarus2015, title = {Structure-based design of novel naproxen derivatives targeting monomeric nucleoprotein of Influenza A virus}, author = {Bogdan Tarus and H\'{e}l{\`{e}}ne Bertrand and Gloria Zedda and Carmelo {Di Primo} and St\'{e}phane Quideau and Anny Slama-Schwok}, url = {https://www.ncbi.nlm.nih.gov/pubmed/25333630 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4548311/}, doi = {10.1080/07391102.2014.979230}, issn = {1538-0254}, year = {2015}, date = {2015-09-01}, journal = {Journal of biomolecular structure & dynamics}, volume = {33}, number = {9}, pages = {1899--1912}, publisher = {Taylor & Francis}, edition = {2014/11/19}, abstract = {The nucleoprotein (NP) binds the viral RNA genome as oligomers assembled with the polymerase in a ribonucleoprotein complex required for transcription and replication of influenza A virus. Novel antiviral candidates targeting the nucleoprotein either induced higher order oligomers or reduced NP oligomerization by targeting the oligomerization loop and blocking its insertion into adjacent nucleoprotein subunit. In this study, we used a different structure-based approach to stabilize monomers of the nucleoprotein by drugs binding in its RNA-binding groove. We recently identified naproxen as a drug competing with RNA binding to NP with antiinflammatory and antiviral effects against influenza A virus. Here, we designed novel derivatives of naproxen by fragment extension for improved binding to NP. Molecular dynamics simulations suggested that among these derivatives, naproxen A and C0 were most promising. Their chemical synthesis is described. Both derivatives markedly stabilized NP monomer against thermal denaturation. Naproxen C0 bound tighter to NP than naproxen at a binding site predicted by MD simulations and shown by competition experiments using wt NP or single-point mutants as determined by surface plasmon resonance. MD simulations suggested that impeded oligomerization and stabilization of monomeric NP is likely to be achieved by drugs binding in the RNA grove and inducing close to their binding site conformational changes of key residues hosting the oligomerization loop as observed for the naproxen derivatives. Naproxen C0 is a potential antiviral candidate blocking influenza nucleoprotein function.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The nucleoprotein (NP) binds the viral RNA genome as oligomers assembled with the polymerase in a ribonucleoprotein complex required for transcription and replication of influenza A virus. Novel antiviral candidates targeting the nucleoprotein either induced higher order oligomers or reduced NP oligomerization by targeting the oligomerization loop and blocking its insertion into adjacent nucleoprotein subunit. In this study, we used a different structure-based approach to stabilize monomers of the nucleoprotein by drugs binding in its RNA-binding groove. We recently identified naproxen as a drug competing with RNA binding to NP with antiinflammatory and antiviral effects against influenza A virus. Here, we designed novel derivatives of naproxen by fragment extension for improved binding to NP. Molecular dynamics simulations suggested that among these derivatives, naproxen A and C0 were most promising. Their chemical synthesis is described. Both derivatives markedly stabilized NP monomer against thermal denaturation. Naproxen C0 bound tighter to NP than naproxen at a binding site predicted by MD simulations and shown by competition experiments using wt NP or single-point mutants as determined by surface plasmon resonance. MD simulations suggested that impeded oligomerization and stabilization of monomeric NP is likely to be achieved by drugs binding in the RNA grove and inducing close to their binding site conformational changes of key residues hosting the oligomerization loop as observed for the naproxen derivatives. Naproxen C0 is a potential antiviral candidate blocking influenza nucleoprotein function. |
Design, Synthesis, and Evaluation of Triazole Derivatives That Induce Nrf2 Dependent Gene Products and Inhibit the Keap1–Nrf2 Protein–Protein Interaction Article de journal Hélène C Bertrand; Marjolein Schaap; Liam Baird; Nikolaos D Georgakopoulos; Adrian Fowkes; Clarisse Thiollier; Hiroko Kachi; Albena T Dinkova-Kostova; Geoff Wells Journal of Medicinal Chemistry, 58 (18), p. 7186–7194, 2015, ISSN: 0022-2623. @article{Bertrand2015, title = {Design, Synthesis, and Evaluation of Triazole Derivatives That Induce Nrf2 Dependent Gene Products and Inhibit the Keap1\textendashNrf2 Protein\textendashProtein Interaction}, author = {H\'{e}l{\`{e}}ne C Bertrand and Marjolein Schaap and Liam Baird and Nikolaos D Georgakopoulos and Adrian Fowkes and Clarisse Thiollier and Hiroko Kachi and Albena T Dinkova-Kostova and Geoff Wells}, url = {https://doi.org/10.1021/acs.jmedchem.5b00602}, doi = {10.1021/acs.jmedchem.5b00602}, issn = {0022-2623}, year = {2015}, date = {2015-09-01}, journal = {Journal of Medicinal Chemistry}, volume = {58}, number = {18}, pages = {7186--7194}, publisher = {American Chemical Society}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Nanometric distance measurements between Mn(II)DOTA centers Article de journal H Y Vincent Ching; P Demay-Drouhard; H C Bertrand; C Policar; L C Tabares; S Un Physical Chemistry Chemical Physics, 17 (36), p. 23368–23377, 2015. @article{VincentChing:2015, title = {Nanometric distance measurements between Mn(II)DOTA centers}, author = {H Y Vincent Ching and P Demay-Drouhard and H C Bertrand and C Policar and L C Tabares and S Un}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84941299721&doi=10.1039%2fc5cp03487f&partnerID=40&md5=bfd7a9aac0fc115147eb207f0fbeb05b}, doi = {10.1039/c5cp03487f}, year = {2015}, date = {2015-01-01}, journal = {Physical Chemistry Chemical Physics}, volume = {17}, number = {36}, pages = {23368--23377}, abstract = {Pulse electron-electron double resonance (PELDOR) is a versatile technique for probing the structures and functions of complex biological systems. Despite the recent interest in high-spin metal-ions for high field/frequency applications, PELDOR measurements of Mn(II) remain relatively underexplored. Here we present Mn(II)-Mn(II) PELDOR distance measurements at 94 GHz on polyproline II (PPII) helices doubly spin-labeled with Mn(II)DOTA, which are distinguished by their small zero-field interaction. The measured Mn-Mn distances and distribution profiles were in good agreement with the expected values from molecular models. Additional features in the frequency-domain spectra became apparent at certain combinations of detect and pump frequencies. Spin-Hamiltonian calculations showed that they likely arose from contributions from the pseudo-secular component of the dipolar interaction that were found to be non-negligible for Mn(II)DOTA. However, the influence of the pseudo-secular component on the distance distribution profiles apparently was limited. The results show the potential of Mn(II)DOTA spin labels for high-field PELDOR distance measurements in proteins and other biological systems. © the Owner Societies 2015.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Pulse electron-electron double resonance (PELDOR) is a versatile technique for probing the structures and functions of complex biological systems. Despite the recent interest in high-spin metal-ions for high field/frequency applications, PELDOR measurements of Mn(II) remain relatively underexplored. Here we present Mn(II)-Mn(II) PELDOR distance measurements at 94 GHz on polyproline II (PPII) helices doubly spin-labeled with Mn(II)DOTA, which are distinguished by their small zero-field interaction. The measured Mn-Mn distances and distribution profiles were in good agreement with the expected values from molecular models. Additional features in the frequency-domain spectra became apparent at certain combinations of detect and pump frequencies. Spin-Hamiltonian calculations showed that they likely arose from contributions from the pseudo-secular component of the dipolar interaction that were found to be non-negligible for Mn(II)DOTA. However, the influence of the pseudo-secular component on the distance distribution profiles apparently was limited. The results show the potential of Mn(II)DOTA spin labels for high-field PELDOR distance measurements in proteins and other biological systems. © the Owner Societies 2015. |
Synthesis, characterization and biological activity of Cu(II), Zn(II) and Re(I) complexes derived from S-benzyldithiocarbazate and 3-acetylcoumarin Article de journal M L Low; G Paulus; P Dorlet; R Guillot; R Rosli; N Delsuc; K A Crouse; C Policar BioMetals, 28 (3), p. 553–566, 2015. @article{Low:2015, title = {Synthesis, characterization and biological activity of Cu(II), Zn(II) and Re(I) complexes derived from S-benzyldithiocarbazate and 3-acetylcoumarin}, author = {M L Low and G Paulus and P Dorlet and R Guillot and R Rosli and N Delsuc and K A Crouse and C Policar}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84939939059&doi=10.1007%2fs10534-015-9831-2&partnerID=40&md5=8d0220a2a88cc9eb122f191d65c87199}, doi = {10.1007/s10534-015-9831-2}, year = {2015}, date = {2015-01-01}, journal = {BioMetals}, volume = {28}, number = {3}, pages = {553--566}, abstract = {Cu(II), Zn(II) and Re(I) complexes have been synthesized with the Schiff base, N′-[1-(2-oxo-2H-chromen-3-yl)-ethylidene]-hydrazinecarbodithioic acid benzyl ester (SBCM-H) which was prepared by condensation of S-benzyldithiocarbazate and 3-acetylcoumarin. The metal complexes were characterized on the basis of various physico-chemical and spectroscopic techniques including elemental analysis and electrochemical studies, and FT-IR, UV-Vis, NMR, EPR and mass spectroscopy. The Schiff base was found to behave as a bidentate ligand coordinating with Cu(II) and Zn(II) in the thiolate form with 1:2 metal to ligand stoichiometry. Crystals suitable for X-ray diffractometry (XRD) were obtained from the reaction of ReCl(CO)5 with SBCM-H forming a centrosymmetric dimeric complex Re2L2(CO)6 linked by Re-S-Re bridges, where S is the thiolate sulfur of the N,S-bidentate ligand. This Re(I) complex is the first metal carbonyl complex with a bidentate dithiocarbazate ligand to have been characterized by XRD. Cytotoxicity assays revealed enhancement of the bioactivity of SBCM-H upon complexation. Both Cu(II) and Re(I) complexes are found to be active against human breast adenocarcinoma cancer cell lines MDA-MB-231 and MCF-7. Graphical Abstract: TOC diagram [Figure not available: see fulltext.] © 2015 Springer Science+Business Media New York.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Cu(II), Zn(II) and Re(I) complexes have been synthesized with the Schiff base, N′-[1-(2-oxo-2H-chromen-3-yl)-ethylidene]-hydrazinecarbodithioic acid benzyl ester (SBCM-H) which was prepared by condensation of S-benzyldithiocarbazate and 3-acetylcoumarin. The metal complexes were characterized on the basis of various physico-chemical and spectroscopic techniques including elemental analysis and electrochemical studies, and FT-IR, UV-Vis, NMR, EPR and mass spectroscopy. The Schiff base was found to behave as a bidentate ligand coordinating with Cu(II) and Zn(II) in the thiolate form with 1:2 metal to ligand stoichiometry. Crystals suitable for X-ray diffractometry (XRD) were obtained from the reaction of ReCl(CO)5 with SBCM-H forming a centrosymmetric dimeric complex Re2L2(CO)6 linked by Re-S-Re bridges, where S is the thiolate sulfur of the N,S-bidentate ligand. This Re(I) complex is the first metal carbonyl complex with a bidentate dithiocarbazate ligand to have been characterized by XRD. Cytotoxicity assays revealed enhancement of the bioactivity of SBCM-H upon complexation. Both Cu(II) and Re(I) complexes are found to be active against human breast adenocarcinoma cancer cell lines MDA-MB-231 and MCF-7. Graphical Abstract: TOC diagram [Figure not available: see fulltext.] © 2015 Springer Science+Business Media New York. |
Metal-carbonyl units for vibrational and luminescence imaging: Towards multimodality Article de journal S Clède; C Policar Chemistry - A European Journal, 21 (3), p. 942–958, 2015. @article{Clede:2015, title = {Metal-carbonyl units for vibrational and luminescence imaging: Towards multimodality}, author = {S Cl\`{e}de and C Policar}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84920784874&doi=10.1002%2fchem.201404600&partnerID=40&md5=eaf7654638733b121ed1fe744e71b7b5}, doi = {10.1002/chem.201404600}, year = {2015}, date = {2015-01-01}, journal = {Chemistry - A European Journal}, volume = {21}, number = {3}, pages = {942--958}, abstract = {Metal-carbonyl complexes are attractive structures for bio-imaging. In addition to unique vibrational properties due to the CO moieties enabling IR and Raman cell imaging, the appropriate choice of ancillary ligands opens up the opportunity for luminescence detection. Through a classification by techniques, past and recent developments in the application of metal-carbonyl complexes for vibrational and luminescence bio-imaging are reviewed. Finally, their potential as bimodal IR and luminescent probes is addressed. © 2015 Wiley-VCH Verlag GmbH & Co. KGaA.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Metal-carbonyl complexes are attractive structures for bio-imaging. In addition to unique vibrational properties due to the CO moieties enabling IR and Raman cell imaging, the appropriate choice of ancillary ligands opens up the opportunity for luminescence detection. Through a classification by techniques, past and recent developments in the application of metal-carbonyl complexes for vibrational and luminescence bio-imaging are reviewed. Finally, their potential as bimodal IR and luminescent probes is addressed. © 2015 Wiley-VCH Verlag GmbH & Co. KGaA. |
An easy-to-detect nona-arginine peptide for epidermal targeting Article de journal S Clède; N Delsuc; C Laugel; F Lambert; C Sandt; A Baillet-Guffroy; C Policar Chemical Communications, 51 (13), p. 2687–2689, 2015. @article{Clede:2015a, title = {An easy-to-detect nona-arginine peptide for epidermal targeting}, author = {S Cl\`{e}de and N Delsuc and C Laugel and F Lambert and C Sandt and A Baillet-Guffroy and C Policar}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84922637409&doi=10.1039%2fc4cc08737b&partnerID=40&md5=a0e333e8498570e4d4ceb500066d9c1e}, doi = {10.1039/c4cc08737b}, year = {2015}, date = {2015-01-01}, journal = {Chemical Communications}, volume = {51}, number = {13}, pages = {2687--2689}, abstract = {A correlative approach combining synchrotron radiation based IR microscopy and fluorescence microscopy enabled the successful detection and quantification of a nona-arginine peptide labelled with a Single Core Multimodal Probe for Imaging (SCoMPI) in skin biopsies. The topical penetration of the conjugate appeared to be time dependent and occurred most probably via the extracellular matrix. This journal is © The Royal Society of Chemistry 2015.}, keywords = {}, pubstate = {published}, tppubtype = {article} } A correlative approach combining synchrotron radiation based IR microscopy and fluorescence microscopy enabled the successful detection and quantification of a nona-arginine peptide labelled with a Single Core Multimodal Probe for Imaging (SCoMPI) in skin biopsies. The topical penetration of the conjugate appeared to be time dependent and occurred most probably via the extracellular matrix. This journal is © The Royal Society of Chemistry 2015. |
Fast magnetically driven electrodeposition of amorphous metal oxide water oxidation catalysts from carbon-coated metallic nanoparticles Article de journal J Zhu; F Lambert; C Policar; F Mavré; B Limoges Journal of Materials Chemistry A, 3 (31), p. 16190–16197, 2015. @article{Zhu:2015, title = {Fast magnetically driven electrodeposition of amorphous metal oxide water oxidation catalysts from carbon-coated metallic nanoparticles}, author = {J Zhu and F Lambert and C Policar and F Mavr\'{e} and B Limoges}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84938100019&doi=10.1039%2fc5ta03430b&partnerID=40&md5=ac4e0e0dc5c94a4c574b14d5b17ac552}, doi = {10.1039/c5ta03430b}, year = {2015}, date = {2015-01-01}, journal = {Journal of Materials Chemistry A}, volume = {3}, number = {31}, pages = {16190--16197}, abstract = {We report a new approach for efficient electrodeposition of amorphous metal oxide water oxidation catalysts on an electrode surface. A catalytic metal-based film was obtained by means of anodic oxidation of metallic nanoparticles, namely carbon-coated cobalt nanoparticles or carbon-coated nickel nanoparticles. Interestingly, these particles are intrinsically conductive and possess magnetic properties which make it easy to collect them on an electrode surface using a simple magnet to form a porous conductive particulate film. Upon anodic polarization in an appropriate electrolyte, the particulate film is rapidly converted into an amorphous metal-based catalytic film that efficiently catalyzes the oxidation of water at neutral pH. Compared to Nocera's method based on anodic electrodeposition of a metal salt in solution, this new electrodeposition strategy offers the key advantage of supplying metal ions in a solid and metallic form, leading to a fast release of high local concentrations of metal ions right at the spot of the film formation (i.e., in the vicinity of the electrode surface). This plays a decisive role in the formation rate of the catalytic film, allowing the deposition of the oxygen-evolving catalyst in a remarkably short-time. Moreover, the methodology can be easily extended to a wide range of metal particles of different nature and sizes, and also to their mixtures, finally offering a new degree of flexibility and opportunities not only in the preparation of metal-based water oxidation catalysts, but also in the preparation of inorganic metal-based catalysts for hydrogen or oxygen evolution. © 2015 The Royal Society of Chemistry.}, keywords = {}, pubstate = {published}, tppubtype = {article} } We report a new approach for efficient electrodeposition of amorphous metal oxide water oxidation catalysts on an electrode surface. A catalytic metal-based film was obtained by means of anodic oxidation of metallic nanoparticles, namely carbon-coated cobalt nanoparticles or carbon-coated nickel nanoparticles. Interestingly, these particles are intrinsically conductive and possess magnetic properties which make it easy to collect them on an electrode surface using a simple magnet to form a porous conductive particulate film. Upon anodic polarization in an appropriate electrolyte, the particulate film is rapidly converted into an amorphous metal-based catalytic film that efficiently catalyzes the oxidation of water at neutral pH. Compared to Nocera's method based on anodic electrodeposition of a metal salt in solution, this new electrodeposition strategy offers the key advantage of supplying metal ions in a solid and metallic form, leading to a fast release of high local concentrations of metal ions right at the spot of the film formation (i.e., in the vicinity of the electrode surface). This plays a decisive role in the formation rate of the catalytic film, allowing the deposition of the oxygen-evolving catalyst in a remarkably short-time. Moreover, the methodology can be easily extended to a wide range of metal particles of different nature and sizes, and also to their mixtures, finally offering a new degree of flexibility and opportunities not only in the preparation of metal-based water oxidation catalysts, but also in the preparation of inorganic metal-based catalysts for hydrogen or oxygen evolution. © 2015 The Royal Society of Chemistry. |