You will find below the list of publications of all the members of the Peptides, Glycoconjugates and Metals in Biology research pole. For individual or theme-specific publications, please consult the research or the personal pages via the members list using the sidebar navigation tool.
2020 |
An easy-to-implement combinatorial approach involving an activity-based assay for the discovery of a peptidyl copper complex mimicking superoxide dismutase Article de journal Amandine Vincent; Jennifer Rodon Fores; Elodie Tauziet; Elodie Quévrain; Ágnes Dancs; Amandine Conte-Daban; Anne-Sophie Bernard; Philippe Pelupessy; Koudedja Coulibaly; Philippe Seksik; Christelle Hureau; Katalin Selmeczi; Clotilde Policar; Nicolas Delsuc Chem. Commun., 56 , p. 399-402, 2020. @article{C9CC07920C, title = {An easy-to-implement combinatorial approach involving an activity-based assay for the discovery of a peptidyl copper complex mimicking superoxide dismutase}, author = {Amandine Vincent and Jennifer Rodon Fores and Elodie Tauziet and Elodie Qu\'{e}vrain and \'{A}gnes Dancs and Amandine Conte-Daban and Anne-Sophie Bernard and Philippe Pelupessy and Koudedja Coulibaly and Philippe Seksik and Christelle Hureau and Katalin Selmeczi and Clotilde Policar and Nicolas Delsuc}, url = {http://dx.doi.org/10.1039/C9CC07920C}, doi = {10.1039/C9CC07920C}, year = {2020}, date = {2020-01-01}, journal = {Chem. Commun.}, volume = {56}, pages = {399-402}, publisher = {The Royal Society of Chemistry}, abstract = {A combinatorial approach using a one-bead-one-compound method and a screening based on a SOD-activity assay was set up for the discovery of an efficient peptidyl copper complex. The complex exhibited good stability constants, suitable redox potentials and excellent intrinsic activity. This complex was further assayed in cells for its antioxidant properties and showed beneficial effects when cells were subjected to oxidative stress.}, keywords = {}, pubstate = {published}, tppubtype = {article} } A combinatorial approach using a one-bead-one-compound method and a screening based on a SOD-activity assay was set up for the discovery of an efficient peptidyl copper complex. The complex exhibited good stability constants, suitable redox potentials and excellent intrinsic activity. This complex was further assayed in cells for its antioxidant properties and showed beneficial effects when cells were subjected to oxidative stress. |
2019 |
Mannose-Coated Fluorescent Lipid Microparticles for Specific Cellular Targeting and Internalization via Glycoreceptor-Induced Phagocytosis Article de journal Blaise Dumat; Lorraine Montel; Léa Pinon; Pascal Matton; Laurent Cattiaux; Jacques Fattaccioli; Jean-Maurice Mallet ACS Applied Bio Materials, 2 , p. 5118-5126, 2019, ISSN: 2576-6422. @article{Dumat2019, title = {Mannose-Coated Fluorescent Lipid Microparticles for Specific Cellular Targeting and Internalization via Glycoreceptor-Induced Phagocytosis}, author = {Blaise Dumat and Lorraine Montel and L\'{e}a Pinon and Pascal Matton and Laurent Cattiaux and Jacques Fattaccioli and Jean-Maurice Mallet}, url = {https://pubs.acs.org/doi/10.1021/acsabm.9b00793}, doi = {10.1021/acsabm.9b00793}, issn = {2576-6422}, year = {2019}, date = {2019-11-01}, journal = {ACS Applied Bio Materials}, volume = {2}, pages = {5118-5126}, publisher = {American Chemical Society}, abstract = {In this work we report on the development of mannose-coated fluorescent lipid microparticles to study the role of C-type lectin membrane receptor in phagocytosis. The micrometric droplets of Soybean oil in water emulsion were functionalized with a tailor-made fluorescent mannolipid. The amphiphilic ligand was built from a mannose unit, a lipid C11 spacer and a naphthalimide fluorophore. The droplets functionalization was monitored by fluorescence microscopy as well as the interaction with concanavalin A which was used as a model lectin in vitro. The use of a monovalent ligand on the surface of emulsion droplets yielded particles with an affinity approximately 40 times higher than that of free mannose. In cellulo, the coated droplets were shown to be specifically internalized by macrophages in a receptor-dependent phagocytic pathway. The naked droplets on the other hand display very little internalization due to their low immunogenicity. This work thus brings evidence that C-type lectin membrane receptors ...}, keywords = {}, pubstate = {published}, tppubtype = {article} } In this work we report on the development of mannose-coated fluorescent lipid microparticles to study the role of C-type lectin membrane receptor in phagocytosis. The micrometric droplets of Soybean oil in water emulsion were functionalized with a tailor-made fluorescent mannolipid. The amphiphilic ligand was built from a mannose unit, a lipid C11 spacer and a naphthalimide fluorophore. The droplets functionalization was monitored by fluorescence microscopy as well as the interaction with concanavalin A which was used as a model lectin in vitro. The use of a monovalent ligand on the surface of emulsion droplets yielded particles with an affinity approximately 40 times higher than that of free mannose. In cellulo, the coated droplets were shown to be specifically internalized by macrophages in a receptor-dependent phagocytic pathway. The naked droplets on the other hand display very little internalization due to their low immunogenicity. This work thus brings evidence that C-type lectin membrane receptors ... |
Oxaliplatin-induced neuropathy: the preventive effect of a new super-oxide dismutase modulator Article de journal Marie-Anne Guillaumot; Olivier Cerles; Hélène C Bertrand; Evelyne Benoit; Carole Nicco; Sandrine Chouzenoux; Alain Schmitt; Frédéric Batteux; Clotilde Policar; Romain Coriat Oncotarget, 10 (60), p. 6418-6431, 2019, ISSN: 1949-2553. @article{OT27248, title = {Oxaliplatin-induced neuropathy: the preventive effect of a new super-oxide dismutase modulator}, author = {Marie-Anne Guillaumot and Olivier Cerles and H\'{e}l\`{e}ne C Bertrand and Evelyne Benoit and Carole Nicco and Sandrine Chouzenoux and Alain Schmitt and Fr\'{e}d\'{e}ric Batteux and Clotilde Policar and Romain Coriat}, url = {https://www.oncotarget.com/article/27248/}, doi = {https://doi.org/10.18632/oncotarget.27248}, issn = {1949-2553}, year = {2019}, date = {2019-01-01}, journal = {Oncotarget}, volume = {10}, number = {60}, pages = {6418-6431}, publisher = {Impact Journals, LLC}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
A Fluorescent False Neurotransmitter as a Dual Electrofluorescent Probe for Secretory Cell Models Article de journal J Pandard; N Pan; D H Ebene; T Le Saux; E Ait-Yahiatène; X Liu; L Grimaud; O Buriez; E Labbé; F Lemaître; M Guille-Collignon ChemPlusChem, 84 (10), p. 1578-1586, 2019, (cited By 0). @article{Pandard20191578, title = {A Fluorescent False Neurotransmitter as a Dual Electrofluorescent Probe for Secretory Cell Models}, author = {J Pandard and N Pan and D H Ebene and T Le Saux and E Ait-Yahiat\`{e}ne and X Liu and L Grimaud and O Buriez and E Labb\'{e} and F Lema\^{i}tre and M Guille-Collignon}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85073931778&doi=10.1002%2fcplu.201900385&partnerID=40&md5=a526291d966e7dc926b44e97c73794b3}, doi = {10.1002/cplu.201900385}, year = {2019}, date = {2019-01-01}, journal = {ChemPlusChem}, volume = {84}, number = {10}, pages = {1578-1586}, note = {cited By 0}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
From Benzofurans to Indoles: Palladium-Catalyzed Reductive Ring-Opening and Closure via β-Phenoxide Elimination Article de journal L A Perego; S Wagschal; R Grüber; P Fleurat-Lessard; L El Kaïm; L Grimaud Advanced Synthesis and Catalysis, 361 (1), p. 151–159, 2019. @article{Perego:2019, title = {From Benzofurans to Indoles: Palladium-Catalyzed Reductive Ring-Opening and Closure via β-Phenoxide Elimination}, author = {L A Perego and S Wagschal and R Gr\"{u}ber and P Fleurat-Lessard and L El Ka\"{i}m and L Grimaud}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85057441313&doi=10.1002%2fadsc.201801225&partnerID=40&md5=56673a99ee9fc8c525272edb560d0ecc}, doi = {10.1002/adsc.201801225}, year = {2019}, date = {2019-01-01}, journal = {Advanced Synthesis and Catalysis}, volume = {361}, number = {1}, pages = {151--159}, abstract = {Benzofurans can undergo ring-opening by a palladium-catalyzed process resulting in C−O bond breaking. Benzofuran-tethered 2-iodoanilines give synthetically interesting 2-(3-indolylmethyl)phenols in an overall reductive process. Mechanistic studies suggest that this unusual reaction proceeds by carbopalladation of benzofuran giving a 3-palladated 2,3-dihydrobenzofuran intermediate, which then fragments by an uncommon trans-elimination of the phenoxide group β to the metal. In this transformation, N,N-diisopropylethylamine (DIPEA) acts as a base and as a reducing agent: it regenerates palladium(0) from palladium(II), thus allowing catalytic turnover. (Figure presented.). © 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim}, keywords = {}, pubstate = {published}, tppubtype = {article} } Benzofurans can undergo ring-opening by a palladium-catalyzed process resulting in C−O bond breaking. Benzofuran-tethered 2-iodoanilines give synthetically interesting 2-(3-indolylmethyl)phenols in an overall reductive process. Mechanistic studies suggest that this unusual reaction proceeds by carbopalladation of benzofuran giving a 3-palladated 2,3-dihydrobenzofuran intermediate, which then fragments by an uncommon trans-elimination of the phenoxide group β to the metal. In this transformation, N,N-diisopropylethylamine (DIPEA) acts as a base and as a reducing agent: it regenerates palladium(0) from palladium(II), thus allowing catalytic turnover. (Figure presented.). © 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim |
Glycoreplica peptides to investigate molecular mechanisms of immune-mediated physiological versus pathological conditions Article de journal A Mazzoleni; J -M Mallet; P Rovero; A M Papini Archives of Biochemistry and Biophysics, 663 , p. 44–53, 2019. @article{Mazzoleni:2019, title = {Glycoreplica peptides to investigate molecular mechanisms of immune-mediated physiological versus pathological conditions}, author = {A Mazzoleni and J -M Mallet and P Rovero and A M Papini}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85059303265&doi=10.1016%2fj.abb.2018.12.030&partnerID=40&md5=054e28b7f9071c163b4af5dcba3d2fcd}, doi = {10.1016/j.abb.2018.12.030}, year = {2019}, date = {2019-01-01}, journal = {Archives of Biochemistry and Biophysics}, volume = {663}, pages = {44--53}, abstract = {Investigation of the role of saccharides and glycoconjugates in mechanisms of immune-mediated physiological and pathological conditions is a hot topic. In fact, in many autoimmune diseases cross-reactivity between sugar moieties exposed on exogenous pathogens and self-molecules has long been hinted. Several peptides have been reported as mimetics of glycans specifically interacting with sugar-binding antibodies. The seek for these glycoreplica peptides is instrumental in characterizing antigen mimicry pathways and their involvement in triggering autoimmunity. Therefore, peptides mimicking glycan-protein interactions are valuable molecular tools to overcome the difficulties of oligosaccharide preparations. The clinical impact of peptide-based probes for autoimmune diseases diagnosis and follow-up is emerging only recently as just the tip of the iceberg of an overlooked potential. Here we provide a brief overview of the relevance of the structural and functional aspects of peptide probes and their mimicry effect in autoimmunity mechanisms for promising applications in diagnostics and therapeutics. © 2019 Elsevier Inc.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Investigation of the role of saccharides and glycoconjugates in mechanisms of immune-mediated physiological and pathological conditions is a hot topic. In fact, in many autoimmune diseases cross-reactivity between sugar moieties exposed on exogenous pathogens and self-molecules has long been hinted. Several peptides have been reported as mimetics of glycans specifically interacting with sugar-binding antibodies. The seek for these glycoreplica peptides is instrumental in characterizing antigen mimicry pathways and their involvement in triggering autoimmunity. Therefore, peptides mimicking glycan-protein interactions are valuable molecular tools to overcome the difficulties of oligosaccharide preparations. The clinical impact of peptide-based probes for autoimmune diseases diagnosis and follow-up is emerging only recently as just the tip of the iceberg of an overlooked potential. Here we provide a brief overview of the relevance of the structural and functional aspects of peptide probes and their mimicry effect in autoimmunity mechanisms for promising applications in diagnostics and therapeutics. © 2019 Elsevier Inc. |
Electroactive fluorescent false neurotransmitter FFN102 partially replaces dopamine in PC12 cell vesicles Article de journal L Hu; A Savy; L Grimaud; M Guille-Collignon; F Lemaître; C Amatore; J Delacotte Biophysical Chemistry, 245 , p. 1–5, 2019. @article{Hu:2019, title = {Electroactive fluorescent false neurotransmitter FFN102 partially replaces dopamine in PC12 cell vesicles}, author = {L Hu and A Savy and L Grimaud and M Guille-Collignon and F Lema\^{i}tre and C Amatore and J Delacotte}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85057201704&doi=10.1016%2fj.bpc.2018.11.001&partnerID=40&md5=28655b4c152ce0fc51fc037feefcff97}, doi = {10.1016/j.bpc.2018.11.001}, year = {2019}, date = {2019-01-01}, journal = {Biophysical Chemistry}, volume = {245}, pages = {1--5}, abstract = {In the last decade, following fluorescent dyes and protein tags, pH sensitive false fluorescent neurotransmitters (FFN) were introduced and were valuable for labeling secretory vesicles and monitoring exocytosis at living cells. In particular, the synthetic analog of neurotransmitters FFN102 was shown to be an electroactive probe. Here, we show that FFN102 is suitable to be used as a bioanalytic probe at the widely used PC12 cell model. FFN102 was uptaken in the secretory vesicles of PC12 cells, partially replacing the endogenous dopamine stored in these vesicles. The different oxidation potentials of dopamine and FFN102 allowed to determine that ca. 12% of dopamine was replaced by FFN102. Moreover, the FFN102 was found to be over released through the initial fusion pore suggesting that it was mostly uptaken in fast diffusion compartment of the vesicles. © 2018 Elsevier B.V.}, keywords = {}, pubstate = {published}, tppubtype = {article} } In the last decade, following fluorescent dyes and protein tags, pH sensitive false fluorescent neurotransmitters (FFN) were introduced and were valuable for labeling secretory vesicles and monitoring exocytosis at living cells. In particular, the synthetic analog of neurotransmitters FFN102 was shown to be an electroactive probe. Here, we show that FFN102 is suitable to be used as a bioanalytic probe at the widely used PC12 cell model. FFN102 was uptaken in the secretory vesicles of PC12 cells, partially replacing the endogenous dopamine stored in these vesicles. The different oxidation potentials of dopamine and FFN102 allowed to determine that ca. 12% of dopamine was replaced by FFN102. Moreover, the FFN102 was found to be over released through the initial fusion pore suggesting that it was mostly uptaken in fast diffusion compartment of the vesicles. © 2018 Elsevier B.V. |
Methylglyoxal, a potent inducer of AGEs, connects between diabetes and cancer Article de journal J Bellier; M -J Nokin; E Lardé; P Karoyan; O Peulen; V Castronovo; A Bellahcène Diabetes Research and Clinical Practice, 148 , p. 200–211, 2019. @article{Bellier:2019, title = {Methylglyoxal, a potent inducer of AGEs, connects between diabetes and cancer}, author = {J Bellier and M -J Nokin and E Lard\'{e} and P Karoyan and O Peulen and V Castronovo and A Bellahc\`{e}ne}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85060445406&doi=10.1016%2fj.diabres.2019.01.002&partnerID=40&md5=0f0783fde807776888c9436e0430c762}, doi = {10.1016/j.diabres.2019.01.002}, year = {2019}, date = {2019-01-01}, journal = {Diabetes Research and Clinical Practice}, volume = {148}, pages = {200--211}, abstract = {Diabetes is one of the most frequent diseases throughout the world and its incidence is predicted to exponentially progress in the future. This metabolic disorder is associated with major complications such as neuropathy, retinopathy, atherosclerosis, and diabetic nephropathy, the severity of which correlates with hyperglycemia, suggesting that they are triggered by high glucose condition. Reducing sugars and reactive carbonyl species such as methylglyoxal (MGO) lead to glycation of proteins, lipids and DNA and the gradual accumulation of advanced glycation end products (AGEs) in cells and tissues. While AGEs are clearly implicated in the pathogenesis of diabetes complications, their potential involvement during malignant tumor development, progression and resistance to therapy is an emerging concept. Meta-analysis studies established that patients with diabetes are at higher risk of developing cancer and show a higher mortality rate than cancer patients free of diabetes. In this review, we highlight the potential connection between hyperglycemia-associated AGEs formation on the one hand and the recent evidence of pro-tumoral effects of MGO stress on the other hand. We also discuss the marked interest in anti-glycation compounds in view of their strategic use to treat diabetic complications but also to protect against augmented cancer risk in patients with diabetes. © 2019}, keywords = {}, pubstate = {published}, tppubtype = {article} } Diabetes is one of the most frequent diseases throughout the world and its incidence is predicted to exponentially progress in the future. This metabolic disorder is associated with major complications such as neuropathy, retinopathy, atherosclerosis, and diabetic nephropathy, the severity of which correlates with hyperglycemia, suggesting that they are triggered by high glucose condition. Reducing sugars and reactive carbonyl species such as methylglyoxal (MGO) lead to glycation of proteins, lipids and DNA and the gradual accumulation of advanced glycation end products (AGEs) in cells and tissues. While AGEs are clearly implicated in the pathogenesis of diabetes complications, their potential involvement during malignant tumor development, progression and resistance to therapy is an emerging concept. Meta-analysis studies established that patients with diabetes are at higher risk of developing cancer and show a higher mortality rate than cancer patients free of diabetes. In this review, we highlight the potential connection between hyperglycemia-associated AGEs formation on the one hand and the recent evidence of pro-tumoral effects of MGO stress on the other hand. We also discuss the marked interest in anti-glycation compounds in view of their strategic use to treat diabetic complications but also to protect against augmented cancer risk in patients with diabetes. © 2019 |
2018 |
New branched amino acids for high affinity dendrimeric DC-SIGN ligands Article de journal L Cattiaux; V Porkolab; F Fieschi; J -M Mallet Bioorganic and Medicinal Chemistry, 26 (5), p. 1006–1015, 2018. @article{Cattiaux:2018, title = {New branched amino acids for high affinity dendrimeric DC-SIGN ligands}, author = {L Cattiaux and V Porkolab and F Fieschi and J -M Mallet}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85042048650&doi=10.1016%2fj.bmc.2017.12.036&partnerID=40&md5=d1f8a5e526fefe44ef305de5415a2eb5}, doi = {10.1016/j.bmc.2017.12.036}, year = {2018}, date = {2018-01-01}, journal = {Bioorganic and Medicinal Chemistry}, volume = {26}, number = {5}, pages = {1006--1015}, abstract = {A branched amino acid was synthesized from methyl glucopyranoside; this amino acid presents three amino groups protected by Fmoc and one acid group and can be used in classic peptide synthesis. In parallel, similar azido terminated blocks were synthesized. Successive coupling reaction and deprotection afforded dendrimers with up to 27 azido functional groups. As an example of application, D-mannose and L-fucose residues were linked through CuAAC coupling and resulting glycodendrimers were evaluated in their interaction with DC-SIGN using SPR competition assay. © 2017 Elsevier Ltd}, keywords = {}, pubstate = {published}, tppubtype = {article} } A branched amino acid was synthesized from methyl glucopyranoside; this amino acid presents three amino groups protected by Fmoc and one acid group and can be used in classic peptide synthesis. In parallel, similar azido terminated blocks were synthesized. Successive coupling reaction and deprotection afforded dendrimers with up to 27 azido functional groups. As an example of application, D-mannose and L-fucose residues were linked through CuAAC coupling and resulting glycodendrimers were evaluated in their interaction with DC-SIGN using SPR competition assay. © 2017 Elsevier Ltd |
Redox switchable rhodamine-ferrocene dyad: Exploring imaging possibilities in cells Article de journal M Čížková; L Cattiaux; J Pandard; M Guille-Collignon; F Lemaître; J Delacotte; J -M Mallet; E Labbé; O Buriez Electrochemistry Communications, 97 , p. 46–50, 2018. @article{Cizkova:2018, title = {Redox switchable rhodamine-ferrocene dyad: Exploring imaging possibilities in cells}, author = {M \v{C}\'{i}\v{z}kov\'{a} and L Cattiaux and J Pandard and M Guille-Collignon and F Lema\^{i}tre and J Delacotte and J -M Mallet and E Labb\'{e} and O Buriez}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85054592456&doi=10.1016%2fj.elecom.2018.10.009&partnerID=40&md5=10a4aed1c89bb6a788a2a260bbd0a818}, doi = {10.1016/j.elecom.2018.10.009}, year = {2018}, date = {2018-01-01}, journal = {Electrochemistry Communications}, volume = {97}, pages = {46--50}, abstract = {An original redox-responsive fluorescent probe combining a rhodamine derivative and a ferrocenyl moiety used as the fluorescence modulator was designed, synthesized and characterized. The fluorescence of this new dyad could be tuned from the redox state of ferrocene, a feature observed both electrochemically and on cancer cells incubated with this probe. © 2018 Elsevier B.V.}, keywords = {}, pubstate = {published}, tppubtype = {article} } An original redox-responsive fluorescent probe combining a rhodamine derivative and a ferrocenyl moiety used as the fluorescence modulator was designed, synthesized and characterized. The fluorescence of this new dyad could be tuned from the redox state of ferrocene, a feature observed both electrochemically and on cancer cells incubated with this probe. © 2018 Elsevier B.V. |
S Cardon; E Sachon; L Carlier; T Drujon; A Walrant; E Alemán-Navarro; V Martínez-Osorio; D Guianvarc’h; S Sagan; Y Fleury; R Marquant; C Piesse; Y Rosenstein; C Auvynet; C Lacombe PLoS ONE, 13 (10), 2018. @article{Cardon:2018, title = {Peptidoglycan potentiates the membrane disrupting effect of the carboxyamidated form of DMS-DA6, a Gram-positive selective antimicrobial peptide isolated from Pachymedusa dacnicolor skin}, author = {S Cardon and E Sachon and L Carlier and T Drujon and A Walrant and E Alem\'{a}n-Navarro and V Mart\'{i}nez-Osorio and D Guianvarc’h and S Sagan and Y Fleury and R Marquant and C Piesse and Y Rosenstein and C Auvynet and C Lacombe}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85055075541&doi=10.1371%2fjournal.pone.0205727&partnerID=40&md5=90ca83358f76849aeaf6bde148982206}, doi = {10.1371/journal.pone.0205727}, year = {2018}, date = {2018-01-01}, journal = {PLoS ONE}, volume = {13}, number = {10}, abstract = {The occurrence of nosocomial infections has been on the rise for the past twenty years. Notably, infections caused by the Gram-positive bacteria Staphylococcus aureus represent a major clinical problem, as an increase in antibiotic multi-resistant strains has accompanied this rise. There is thus a crucial need to find and characterize new antibiotics against Gram-positive bacteria, and against antibiotic-resistant strains in general. We identified a new dermaseptin, DMS-DA6, produced by the skin of the Mexican frog Pachymedusa dacnicolor, with specific antibacterial activity against Gram-positive bacteria. This peptide is particularly effective against two multiple drug-resistant strains Enterococcus faecium BM4147 and Staphylococcus aureus DAR5829, and has no hemolytic activity. DMS-DA6 is naturally produced with the C-terminal carboxyl group in either the free or amide forms. By using Gram-positive model membranes and different experimental approaches, we showed that both forms of the peptide adopt an ∞-helical fold and have the same ability to insert into, and to disorganize a membrane composed of anionic lipids. However, the bactericidal capacity of DMS-DA6-NH2 was consistently more potent than that of DMS-DA6-OH. Remarkably, rather than resulting from the interaction with the negatively charged lipids of the membrane, or from a more stable conformation towards proteolysis, the increased capacity to permeabilize the membrane of Gram-positive bacteria of the carboxyamidated form of DMS-DA6 was found to result from its enhanced ability to interact with peptidoglycan. © 2018 Cardon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The occurrence of nosocomial infections has been on the rise for the past twenty years. Notably, infections caused by the Gram-positive bacteria Staphylococcus aureus represent a major clinical problem, as an increase in antibiotic multi-resistant strains has accompanied this rise. There is thus a crucial need to find and characterize new antibiotics against Gram-positive bacteria, and against antibiotic-resistant strains in general. We identified a new dermaseptin, DMS-DA6, produced by the skin of the Mexican frog Pachymedusa dacnicolor, with specific antibacterial activity against Gram-positive bacteria. This peptide is particularly effective against two multiple drug-resistant strains Enterococcus faecium BM4147 and Staphylococcus aureus DAR5829, and has no hemolytic activity. DMS-DA6 is naturally produced with the C-terminal carboxyl group in either the free or amide forms. By using Gram-positive model membranes and different experimental approaches, we showed that both forms of the peptide adopt an ∞-helical fold and have the same ability to insert into, and to disorganize a membrane composed of anionic lipids. However, the bactericidal capacity of DMS-DA6-NH2 was consistently more potent than that of DMS-DA6-OH. Remarkably, rather than resulting from the interaction with the negatively charged lipids of the membrane, or from a more stable conformation towards proteolysis, the increased capacity to permeabilize the membrane of Gram-positive bacteria of the carboxyamidated form of DMS-DA6 was found to result from its enhanced ability to interact with peptidoglycan. © 2018 Cardon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
Increased Efficiency of Dye-Sensitized Solar Cells by Incorporation of a π Spacer in Donor–Acceptor Zinc Porphyrins Bearing Cyanoacrylic Acid as an Anchoring Group Article de journal S Panagiotakis; E Giannoudis; A Charisiadis; R Paravatou; M -E Lazaridi; M Kandyli; K Ladomenou; P A Angaridis; H C Bertrand; G D Sharma; A G Coutsolelos European Journal of Inorganic Chemistry, 2018 (20), p. 2369–2379, 2018. @article{Panagiotakis:2018, title = {Increased Efficiency of Dye-Sensitized Solar Cells by Incorporation of a π Spacer in Donor\textendashAcceptor Zinc Porphyrins Bearing Cyanoacrylic Acid as an Anchoring Group}, author = {S Panagiotakis and E Giannoudis and A Charisiadis and R Paravatou and M -E Lazaridi and M Kandyli and K Ladomenou and P A Angaridis and H C Bertrand and G D Sharma and A G Coutsolelos}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85044864237&doi=10.1002%2fejic.201800123&partnerID=40&md5=1a3cfeb98ec9917efc3f7e5dbcd02977}, doi = {10.1002/ejic.201800123}, year = {2018}, date = {2018-01-01}, journal = {European Journal of Inorganic Chemistry}, volume = {2018}, number = {20}, pages = {2369--2379}, abstract = {Two novel porphyrins, ZnP(SP)CNCOOH and ZnPCNCOOH, bearing cyanoacrylic acid as an anchoring group were synthesized. Porphyrin ZnP(SP)CNCOOH contains a π-conjugated spacer (SP) for improved electronic communication between the dye and the TiO2 electrode. The spacer bears polyethylene glycol chains to prevent dye aggregation and to enhance solubility of the dye. Electrochemical measurements and theoretical calculations suggest that both porphyrins are promising sensitizers for dye-sensitized solar cells (DSSCs), as their molecular orbital energy levels favor electron injection and dye regeneration. Solar cells sensitized by ZnP(SP)CNCOOH and ZnPCNCOOH show power conversion efficiencies of 7.61 and 5.02 %, respectively. Photovoltaic measurements (J\textendashV curves and incident photon to current conversion efficiency spectra) show that higher short-circuit current (Jsc) and open-circuit voltage (Voc) values are reached for the solar cell based on ZnP(SP)CNCOOH. This can be mainly ascribed to suppressed charge recombination, as indicated by their electrochemical impedance spectra. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim}, keywords = {}, pubstate = {published}, tppubtype = {article} } Two novel porphyrins, ZnP(SP)CNCOOH and ZnPCNCOOH, bearing cyanoacrylic acid as an anchoring group were synthesized. Porphyrin ZnP(SP)CNCOOH contains a π-conjugated spacer (SP) for improved electronic communication between the dye and the TiO2 electrode. The spacer bears polyethylene glycol chains to prevent dye aggregation and to enhance solubility of the dye. Electrochemical measurements and theoretical calculations suggest that both porphyrins are promising sensitizers for dye-sensitized solar cells (DSSCs), as their molecular orbital energy levels favor electron injection and dye regeneration. Solar cells sensitized by ZnP(SP)CNCOOH and ZnPCNCOOH show power conversion efficiencies of 7.61 and 5.02 %, respectively. Photovoltaic measurements (J–V curves and incident photon to current conversion efficiency spectra) show that higher short-circuit current (Jsc) and open-circuit voltage (Voc) values are reached for the solar cell based on ZnP(SP)CNCOOH. This can be mainly ascribed to suppressed charge recombination, as indicated by their electrochemical impedance spectra. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim |
Clarifying the Copper Coordination Environment in a de Novo Designed Red Copper Protein Article de journal K J Koebke; L Ruckthong; J L Meagher; E Mathieu; J Harland; A Deb; N Lehnert; C Policar; C Tard; J E Penner-Hahn; J A Stuckey; V L Pecoraro Inorganic Chemistry, 57 (19), p. 12291–12302, 2018. @article{Koebke:2018, title = {Clarifying the Copper Coordination Environment in a de Novo Designed Red Copper Protein}, author = {K J Koebke and L Ruckthong and J L Meagher and E Mathieu and J Harland and A Deb and N Lehnert and C Policar and C Tard and J E Penner-Hahn and J A Stuckey and V L Pecoraro}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85053716026&doi=10.1021%2facs.inorgchem.8b01989&partnerID=40&md5=1ff4fcf88039da93326134a5ecf32822}, doi = {10.1021/acs.inorgchem.8b01989}, year = {2018}, date = {2018-01-01}, journal = {Inorganic Chemistry}, volume = {57}, number = {19}, pages = {12291--12302}, abstract = {Cupredoxins are copper-dependent electron-transfer proteins that can be categorized as blue, purple, green, and red depending on the spectroscopic properties of the Cu(II) bound forms. Interestingly, despite significantly different first coordination spheres and nuclearity, all cupredoxins share a common Greek Key β-sheet fold. We have previously reported the design of a red copper protein within a completely distinct three-helical bundle protein, α3DChC2.(1)While this design demonstrated that a β-barrel fold was not requisite to recapitulate the properties of a native cupredoxin center, the parent peptide α3D was not sufficiently stable to allow further study through additional mutations. Here we present the design of an elongated protein GRANDα3D (GRα3D) with ΔGu = -11.4 kcal/mol compared to the original design's -5.1 kcal/mol. Diffraction quality crystals were grown of GRα3D (a first for an α3D peptide) and solved to a resolution of 1.34 r{A}. Examination of this structure suggested that Glu41 might interact with the Cu in our previously reported red copper protein. The previous bis(histidine)(cysteine) site (GRα3DChC2) was designed into this new scaffold and a series of variant constructs were made to explore this hypothesis. Mutation studies around Glu41 not only prove the proposed interaction, but also enabled tuning of the constructs' hyperfine coupling constant from 160 to 127 × 10-4 cm-1. X-ray absorption spectroscopy analysis is consistent with these hyperfine coupling differences being the result of variant 4p mixing related to coordination geometry changes. These studies not only prove that an Glu41-Cu interaction leads to the α3DChC2 construct's red copper protein like spectral properties, but also exemplify the exact control one can have in a de novo construct to tune the properties of an electron-transfer Cu site. Copyright © 2018 American Chemical Society.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Cupredoxins are copper-dependent electron-transfer proteins that can be categorized as blue, purple, green, and red depending on the spectroscopic properties of the Cu(II) bound forms. Interestingly, despite significantly different first coordination spheres and nuclearity, all cupredoxins share a common Greek Key β-sheet fold. We have previously reported the design of a red copper protein within a completely distinct three-helical bundle protein, α3DChC2.(1)While this design demonstrated that a β-barrel fold was not requisite to recapitulate the properties of a native cupredoxin center, the parent peptide α3D was not sufficiently stable to allow further study through additional mutations. Here we present the design of an elongated protein GRANDα3D (GRα3D) with ΔGu = -11.4 kcal/mol compared to the original design's -5.1 kcal/mol. Diffraction quality crystals were grown of GRα3D (a first for an α3D peptide) and solved to a resolution of 1.34 Å. Examination of this structure suggested that Glu41 might interact with the Cu in our previously reported red copper protein. The previous bis(histidine)(cysteine) site (GRα3DChC2) was designed into this new scaffold and a series of variant constructs were made to explore this hypothesis. Mutation studies around Glu41 not only prove the proposed interaction, but also enabled tuning of the constructs' hyperfine coupling constant from 160 to 127 × 10-4 cm-1. X-ray absorption spectroscopy analysis is consistent with these hyperfine coupling differences being the result of variant 4p mixing related to coordination geometry changes. These studies not only prove that an Glu41-Cu interaction leads to the α3DChC2 construct's red copper protein like spectral properties, but also exemplify the exact control one can have in a de novo construct to tune the properties of an electron-transfer Cu site. Copyright © 2018 American Chemical Society. |
Ferrocifens labelled with an infrared rhenium tricarbonyl tag: Synthesis, antiproliferative activity, quantification and nano IR mapping in cancer cells Article de journal Y Wang; F Heinemann; S Top; A Dazzi; C Policar; L Henry; F Lambert; G Jaouen; M Salmain; A Vessieres Dalton Transactions, 47 (29), p. 9824–9833, 2018. @article{Wang:2018c, title = {Ferrocifens labelled with an infrared rhenium tricarbonyl tag: Synthesis, antiproliferative activity, quantification and nano IR mapping in cancer cells}, author = {Y Wang and F Heinemann and S Top and A Dazzi and C Policar and L Henry and F Lambert and G Jaouen and M Salmain and A Vessieres}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85050854664&doi=10.1039%2fc8dt01582a&partnerID=40&md5=1eb695f8b77ceadad719c5ab75b11480}, doi = {10.1039/c8dt01582a}, year = {2018}, date = {2018-01-01}, journal = {Dalton Transactions}, volume = {47}, number = {29}, pages = {9824--9833}, abstract = {Antiproliferative activities of several members of the ferrocifen family, both in vitro and in vivo, are well documented although their precise location in cancer cells has not yet been elucidated. However, two different infrared imaging techniques have been used to map the non-cytotoxic cyrhetrenyl analogue of ferrociphenol in a single cell. This observation prompted us to tag two ferrocifens with a cyrhetrenyl unit [CpRe(CO)3; Cp = η5-cyclopentadienyl] by grafting it, via an ester bond, either to one of the phenols (4, 5) or to the hydroxypropyl chain (6). Complexes 4-6 retained a high cytotoxicity on breast cancer cells (MDA-MB-231) with IC50 values in the range 0.32-2.5 μM. Transmission IR spectroscopy was used to quantify the amount of cyrhetrenyl tag present in cells incubated with 5 or 6. The results show that after a 1-hour incubation of cells at 37 °C, complexes 5 and 6 are mainly present within cells while only a limited percentage, quantified by ICP-OES, remained in the incubation medium. AFM-IR spectroscopy, a technique coupling infrared irradiation with near-field AFM detection, was used to map the cyrhetrenyl unit in a single MDA-MB-231 cell, incubated at 37 °C for 1 hour with 10 μM of 6. The results show that signal distribution of the characteristic band of the Re(CO)3 entity at 1950 cm-1 matched those of amide and phosphate, thus indicating a location of the complex mainly in the cell nucleus. © 2018 The Royal Society of Chemistry.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Antiproliferative activities of several members of the ferrocifen family, both in vitro and in vivo, are well documented although their precise location in cancer cells has not yet been elucidated. However, two different infrared imaging techniques have been used to map the non-cytotoxic cyrhetrenyl analogue of ferrociphenol in a single cell. This observation prompted us to tag two ferrocifens with a cyrhetrenyl unit [CpRe(CO)3; Cp = η5-cyclopentadienyl] by grafting it, via an ester bond, either to one of the phenols (4, 5) or to the hydroxypropyl chain (6). Complexes 4-6 retained a high cytotoxicity on breast cancer cells (MDA-MB-231) with IC50 values in the range 0.32-2.5 μM. Transmission IR spectroscopy was used to quantify the amount of cyrhetrenyl tag present in cells incubated with 5 or 6. The results show that after a 1-hour incubation of cells at 37 °C, complexes 5 and 6 are mainly present within cells while only a limited percentage, quantified by ICP-OES, remained in the incubation medium. AFM-IR spectroscopy, a technique coupling infrared irradiation with near-field AFM detection, was used to map the cyrhetrenyl unit in a single MDA-MB-231 cell, incubated at 37 °C for 1 hour with 10 μM of 6. The results show that signal distribution of the characteristic band of the Re(CO)3 entity at 1950 cm-1 matched those of amide and phosphate, thus indicating a location of the complex mainly in the cell nucleus. © 2018 The Royal Society of Chemistry. |
Graftable SCoMPIs enable the labeling and X-ray fluorescence imaging of proteins Article de journal S Hostachy; M Masuda; T Miki; I Hamachi; S Sagan; O Lequin; K Medjoubi; A Somogyi; N Delsuc; C Policar Chemical Science, 9 (19), p. 4483–4487, 2018. @article{Hostachy:2018, title = {Graftable SCoMPIs enable the labeling and X-ray fluorescence imaging of proteins}, author = {S Hostachy and M Masuda and T Miki and I Hamachi and S Sagan and O Lequin and K Medjoubi and A Somogyi and N Delsuc and C Policar}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85047244059&doi=10.1039%2fc8sc00886h&partnerID=40&md5=4625eaa891ccc665a2357b73e20e3541}, doi = {10.1039/c8sc00886h}, year = {2018}, date = {2018-01-01}, journal = {Chemical Science}, volume = {9}, number = {19}, pages = {4483--4487}, abstract = {Bio-imaging techniques alternative to fluorescence microscopy are gaining increasing interest as complementary tools to visualize and analyze biological systems. Among them, X-ray fluorescence microspectroscopy provides information on the local content and distribution of heavy elements (Z ≥ 14) in cells or biological samples. In this context, similar tools to those developed for fluorescence microscopy are desired, including chemical probes or tags. In this work, we study rhenium complexes as a convenient and sensitive probe for X-ray fluorescence microspectroscopy. We demonstrate their ability to label and sense exogenously incubated or endogenous proteins inside cells. © The Royal Society of Chemistry 2018.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Bio-imaging techniques alternative to fluorescence microscopy are gaining increasing interest as complementary tools to visualize and analyze biological systems. Among them, X-ray fluorescence microspectroscopy provides information on the local content and distribution of heavy elements (Z ≥ 14) in cells or biological samples. In this context, similar tools to those developed for fluorescence microscopy are desired, including chemical probes or tags. In this work, we study rhenium complexes as a convenient and sensitive probe for X-ray fluorescence microspectroscopy. We demonstrate their ability to label and sense exogenously incubated or endogenous proteins inside cells. © The Royal Society of Chemistry 2018. |
Labeling of Hyaluronic Acids with a Rhenium-tricarbonyl Tag and Percutaneous Penetration Studied by Multimodal Imaging Article de journal L Henry; N Delsuc; C Laugel; F Lambert; C Sandt; S Hostachy; A -S Bernard; H C Bertrand; L Grimaud; A Baillet-Guffroy; C Policar Bioconjugate Chemistry, 29 (4), p. 987–991, 2018. @article{Henry:2018, title = {Labeling of Hyaluronic Acids with a Rhenium-tricarbonyl Tag and Percutaneous Penetration Studied by Multimodal Imaging}, author = {L Henry and N Delsuc and C Laugel and F Lambert and C Sandt and S Hostachy and A -S Bernard and H C Bertrand and L Grimaud and A Baillet-Guffroy and C Policar}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85045549363&doi=10.1021%2facs.bioconjchem.7b00825&partnerID=40&md5=87140714a264358836c5f4c7734e49a3}, doi = {10.1021/acs.bioconjchem.7b00825}, year = {2018}, date = {2018-01-01}, journal = {Bioconjugate Chemistry}, volume = {29}, number = {4}, pages = {987--991}, abstract = {Hyaluronic acids were labeled with a rhenium-tricarbonyl used as single core multimodal probe for imaging and their penetration into human skin biopsies was studied using IR microscopy and fluorescence imaging (labeled SCoMPI). The penetration was shown to be dependent on the molecular weight of the molecule and limited to the upper layer of the skin. © 2018 American Chemical Society.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Hyaluronic acids were labeled with a rhenium-tricarbonyl used as single core multimodal probe for imaging and their penetration into human skin biopsies was studied using IR microscopy and fluorescence imaging (labeled SCoMPI). The penetration was shown to be dependent on the molecular weight of the molecule and limited to the upper layer of the skin. © 2018 American Chemical Society. |
A Metallo Pro-Drug to Target CuII in the Context of Alzheimer's Disease Article de journal A Conte-Daban; V Ambike; R Guillot; N Delsuc; C Policar; C Hureau Chemistry - A European Journal, 24 (20), p. 5095–5099, 2018. @article{Conte-Daban:2018, title = {A Metallo Pro-Drug to Target CuII in the Context of Alzheimer's Disease}, author = {A Conte-Daban and V Ambike and R Guillot and N Delsuc and C Policar and C Hureau}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85045131927&doi=10.1002%2fchem.201706049&partnerID=40&md5=5dc310a9e12535e296ba5429250159d3}, doi = {10.1002/chem.201706049}, year = {2018}, date = {2018-01-01}, journal = {Chemistry - A European Journal}, volume = {24}, number = {20}, pages = {5095--5099}, abstract = {Alzheimer's disease and oxidative stress are connected. In the present communication, we report the use of a MnII-based superoxide dismutase (SOD) mimic ([MnII(L)]+, 1+) as a pro-drug candidate to target CuII-associated events, namely, CuII-induced formation of reactive oxygen species (ROS) and modulation of the amyloid-β (Aβ) peptide aggregation. Complex 1+ is able to remove CuII from Aβ, stop ROS and prevent alteration of Aβ aggregation as would do the corresponding free ligand LH. Using 1+ instead of LH in further biological applications would have the double advantage to avoid the cell toxicity of LH and to benefit from its proved SOD-like activity. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim}, keywords = {}, pubstate = {published}, tppubtype = {article} } Alzheimer's disease and oxidative stress are connected. In the present communication, we report the use of a MnII-based superoxide dismutase (SOD) mimic ([MnII(L)]+, 1+) as a pro-drug candidate to target CuII-associated events, namely, CuII-induced formation of reactive oxygen species (ROS) and modulation of the amyloid-β (Aβ) peptide aggregation. Complex 1+ is able to remove CuII from Aβ, stop ROS and prevent alteration of Aβ aggregation as would do the corresponding free ligand LH. Using 1+ instead of LH in further biological applications would have the double advantage to avoid the cell toxicity of LH and to benefit from its proved SOD-like activity. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim |
Macrophage-derived superoxide production and antioxidant response following skeletal muscle injury Article de journal E Le Moal; G Juban; A S Bernard; T Varga; C Policar; B Chazaud; R Mounier Free Radical Biology and Medicine, 120 , p. 33–40, 2018. @article{LeMoal:2018, title = {Macrophage-derived superoxide production and antioxidant response following skeletal muscle injury}, author = {E Le Moal and G Juban and A S Bernard and T Varga and C Policar and B Chazaud and R Mounier}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85044047057&doi=10.1016%2fj.freeradbiomed.2018.02.024&partnerID=40&md5=3d7a016c57bd52dfee180ac22ee70ae8}, doi = {10.1016/j.freeradbiomed.2018.02.024}, year = {2018}, date = {2018-01-01}, journal = {Free Radical Biology and Medicine}, volume = {120}, pages = {33--40}, abstract = {Macrophages are key players of immunity that display different functions according to their activation states. In a regenerative context, pro-inflammatory macrophages (Ly6Cpos) are involved in the mounting of the inflammatory response whereas anti-inflammatory macrophages (Ly6Cneg) dampen the inflammation and promote tissue repair. Reactive oxygen species (ROS) production is a hallmark of tissue injury and of subsequent inflammation as described in a bacterial challenge context. However, whether macrophages produce ROS following a sterile tissue injury is uncertain. In this study, we used complementary in vitro, ex vivo and in vivo experiments in mouse to show that macrophages do not release ROS following a sterile injury in skeletal muscle. Furthermore, expression profiles of genes involved in the response to oxidative stress in Ly6Cpos and Ly6Cneg macrophage subsets did not indicate any antioxidant response in this context. Finally, in vivo, pharmacological antioxidant supplementation with N-Acetyl-cysteine (NAC) following skeletal muscle injury did not alter macrophage phenotype during skeletal muscle regeneration. Overall, these results indicate that following a sterile injury, macrophage-derived ROS release is not involved in the regulation of the inflammatory response in the regenerating skeletal muscle. © 2018 Elsevier Inc.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Macrophages are key players of immunity that display different functions according to their activation states. In a regenerative context, pro-inflammatory macrophages (Ly6Cpos) are involved in the mounting of the inflammatory response whereas anti-inflammatory macrophages (Ly6Cneg) dampen the inflammation and promote tissue repair. Reactive oxygen species (ROS) production is a hallmark of tissue injury and of subsequent inflammation as described in a bacterial challenge context. However, whether macrophages produce ROS following a sterile tissue injury is uncertain. In this study, we used complementary in vitro, ex vivo and in vivo experiments in mouse to show that macrophages do not release ROS following a sterile injury in skeletal muscle. Furthermore, expression profiles of genes involved in the response to oxidative stress in Ly6Cpos and Ly6Cneg macrophage subsets did not indicate any antioxidant response in this context. Finally, in vivo, pharmacological antioxidant supplementation with N-Acetyl-cysteine (NAC) following skeletal muscle injury did not alter macrophage phenotype during skeletal muscle regeneration. Overall, these results indicate that following a sterile injury, macrophage-derived ROS release is not involved in the regulation of the inflammatory response in the regenerating skeletal muscle. © 2018 Elsevier Inc. |
GPCR modulation in breast cancer Article de journal R Lappano; Y Jacquot; M Maggiolini International Journal of Molecular Sciences, 19 (12), 2018. @article{Lappano:2018, title = {GPCR modulation in breast cancer}, author = {R Lappano and Y Jacquot and M Maggiolini}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85057977359&doi=10.3390%2fijms19123840&partnerID=40&md5=2eda31a7898bc134fec0136f301bf16a}, doi = {10.3390/ijms19123840}, year = {2018}, date = {2018-01-01}, journal = {International Journal of Molecular Sciences}, volume = {19}, number = {12}, abstract = {Breast cancer is the most prevalent cancer found in women living in developed countries. Endocrine therapy is the mainstay of treatment for hormone-responsive breast tumors (about 70% of all breast cancers) and implies the use of selective estrogen receptor modulators and aromatase inhibitors. In contrast, triple-negative breast cancer (TNBC), a highly heterogeneous disease that may account for up to 24% of all newly diagnosed cases, is hormone-independent and characterized by a poor prognosis. As drug resistance is common in all breast cancer subtypes despite the different treatment modalities, novel therapies targeting signaling transduction pathways involved in the processes of breast carcinogenesis, tumor promotion and metastasis have been subject to accurate consideration. G protein-coupled receptors (GPCRs) are the largest family of cell-surface receptors involved in the development and progression of many tumors including breast cancer. Here we discuss data regarding GPCR-mediated signaling, pharmacological properties and biological outputs toward breast cancer tumorigenesis and metastasis. Furthermore, we address several drugs that have shown an unexpected opportunity to interfere with GPCR-based breast tumorigenic signals. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Breast cancer is the most prevalent cancer found in women living in developed countries. Endocrine therapy is the mainstay of treatment for hormone-responsive breast tumors (about 70% of all breast cancers) and implies the use of selective estrogen receptor modulators and aromatase inhibitors. In contrast, triple-negative breast cancer (TNBC), a highly heterogeneous disease that may account for up to 24% of all newly diagnosed cases, is hormone-independent and characterized by a poor prognosis. As drug resistance is common in all breast cancer subtypes despite the different treatment modalities, novel therapies targeting signaling transduction pathways involved in the processes of breast carcinogenesis, tumor promotion and metastasis have been subject to accurate consideration. G protein-coupled receptors (GPCRs) are the largest family of cell-surface receptors involved in the development and progression of many tumors including breast cancer. Here we discuss data regarding GPCR-mediated signaling, pharmacological properties and biological outputs toward breast cancer tumorigenesis and metastasis. Furthermore, we address several drugs that have shown an unexpected opportunity to interfere with GPCR-based breast tumorigenic signals. © 2018 by the authors. Licensee MDPI, Basel, Switzerland. |
Rhenium tricarbonyl complexes with arenethiolate axial ligands Article de journal M He; H Y V Ching; C Policar; H C Bertrand New Journal of Chemistry, 42 (14), p. 11312–11323, 2018. @article{He:2018, title = {Rhenium tricarbonyl complexes with arenethiolate axial ligands}, author = {M He and H Y V Ching and C Policar and H C Bertrand}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85049750977&doi=10.1039%2fc8nj01960f&partnerID=40&md5=eac4613cb3f849f5a149c72a46384912}, doi = {10.1039/c8nj01960f}, year = {2018}, date = {2018-01-01}, journal = {New Journal of Chemistry}, volume = {42}, number = {14}, pages = {11312--11323}, abstract = {Due to their unique electronic and photophysical properties, rhenium(i) fac-tricarbonyl complexes of general formula [Re(NtextasciicircumN)(CO)3X]n+ have been arousing constant interest in many diverse fields and applications, such as CO2 (photo)electroreduction, organic light emitting diodes and materials, sensors, biological applications and bio-imaging. The photophysical properties of [Re(NtextasciicircumN)(CO)3X]n+ complexes can be modulated by structural variations of the ligands. Modifications of the NtextasciicircumN diimine ligand and of the axial X ligand have been deeply investigated. However, thiolate ligands have scarcely been used in the synthesis of rhenium tricarbonyl complexes. We describe the synthesis of a series of Pyta and Tapy-based Re(i) fac-tricarbonyl complexes with diversely para-substituted arenethiolates in the coordination sphere and report on the electrochemical, photophysical properties and DFT studies of such complexes. © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Due to their unique electronic and photophysical properties, rhenium(i) fac-tricarbonyl complexes of general formula [Re(NtextasciicircumN)(CO)3X]n+ have been arousing constant interest in many diverse fields and applications, such as CO2 (photo)electroreduction, organic light emitting diodes and materials, sensors, biological applications and bio-imaging. The photophysical properties of [Re(NtextasciicircumN)(CO)3X]n+ complexes can be modulated by structural variations of the ligands. Modifications of the NtextasciicircumN diimine ligand and of the axial X ligand have been deeply investigated. However, thiolate ligands have scarcely been used in the synthesis of rhenium tricarbonyl complexes. We describe the synthesis of a series of Pyta and Tapy-based Re(i) fac-tricarbonyl complexes with diversely para-substituted arenethiolates in the coordination sphere and report on the electrochemical, photophysical properties and DFT studies of such complexes. © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique. |
Probing the in-air growth of large area of 3D functional structures into a 2D supramolecular nanoporous network Article de journal R Brisse; D Guianvarc'h; C Mansuy; S Sagan; D Kreher; L Sosa-Vargas; L Hamitouche; V Humblot; I Arfaoui; V Labet; C Paris; C Petit; A -J Attias Chemical Communications, 54 (72), p. 10068–10071, 2018. @article{Brisse:2018, title = {Probing the in-air growth of large area of 3D functional structures into a 2D supramolecular nanoporous network}, author = {R Brisse and D Guianvarc'h and C Mansuy and S Sagan and D Kreher and L Sosa-Vargas and L Hamitouche and V Humblot and I Arfaoui and V Labet and C Paris and C Petit and A -J Attias}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85053165096&doi=10.1039%2fC8CC06125D&partnerID=40&md5=0fc8e0f5c85451c72df0638b78a31224}, doi = {10.1039/C8CC06125D}, year = {2018}, date = {2018-01-01}, journal = {Chemical Communications}, volume = {54}, number = {72}, pages = {10068--10071}, abstract = {Surface-confined host-guest chemistry at the air/solid interface is used for trapping a functionalized 3D Zn-phthalocyanine complex into a 2D porous supramolecular template allowing the large area functionalization of an sp2-hybridized carbon-based substrate as evidenced by STM, resonance Raman spectroscopy, and water contact angle measurements. © The Royal Society of Chemistry.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Surface-confined host-guest chemistry at the air/solid interface is used for trapping a functionalized 3D Zn-phthalocyanine complex into a 2D porous supramolecular template allowing the large area functionalization of an sp2-hybridized carbon-based substrate as evidenced by STM, resonance Raman spectroscopy, and water contact angle measurements. © The Royal Society of Chemistry. |
Electrochemical switching fluorescence emission in rhodamine derivatives Article de journal Martina Č'ižková; Laurent Cattiaux; Jean-Maurice Mallet; Eric Labbé; Olivier Buriez Electrochimica Acta, 260 , p. 589–597, 2018. @article{vcivzkova2018electrochemical, title = {Electrochemical switching fluorescence emission in rhodamine derivatives}, author = {Martina {\v{C}}{'i}{\v{z}}kov\'{a} and Laurent Cattiaux and Jean-Maurice Mallet and Eric Labb\'{e} and Olivier Buriez}, year = {2018}, date = {2018-01-01}, journal = {Electrochimica Acta}, volume = {260}, pages = {589--597}, publisher = {Elsevier}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Redox switchable rhodamine-ferrocene dyad: Exploring imaging possibilities in cells Article de journal Martina Č'ižková; Laurent Cattiaux; Justine Pandard; Manon Guille-Collignon; Frédéric Lema^itre; Jér^ome Delacotte; Jean-Maurice Mallet; Eric Labbé; Olivier Buriez Electrochemistry Communications, 97 , p. 46–50, 2018. @article{vcivzkova2018redox, title = {Redox switchable rhodamine-ferrocene dyad: Exploring imaging possibilities in cells}, author = {Martina {\v{C}}{'i}{\v{z}}kov\'{a} and Laurent Cattiaux and Justine Pandard and Manon Guille-Collignon and Fr\'{e}d\'{e}ric Lema{^i}tre and J\'{e}r{^o}me Delacotte and Jean-Maurice Mallet and Eric Labb\'{e} and Olivier Buriez}, year = {2018}, date = {2018-01-01}, journal = {Electrochemistry Communications}, volume = {97}, pages = {46--50}, publisher = {Elsevier}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Synthesis, Oligonucleotide Incorporation and Fluorescence Properties in DNA of a Bicyclic Thymine Analogue Article de journal Christopher P Lawson; Anders F Füchtbauer; Moa S Wranne; Tristan Giraud; Thomas Floyd; Blaise Dumat; Nicolai K Andersen; Afaf H. El-Sagheer; Tom Brown; Henrik Gradén; Marcus L Wilhelmsson; Morten Grøtli Scientific Reports, 8 (1), p. 1-9, 2018, ISSN: 4159801831897. @article{Lawson:2018, title = {Synthesis, Oligonucleotide Incorporation and Fluorescence Properties in DNA of a Bicyclic Thymine Analogue}, author = {Christopher P Lawson and Anders F F\"{u}chtbauer and Moa S Wranne and Tristan Giraud and Thomas Floyd and Blaise Dumat and Nicolai K Andersen and Afaf {H. El-Sagheer} and Tom Brown and Henrik Grad\'{e}n and Marcus L Wilhelmsson and Morten Gr\otli}, doi = {10.1038/s41598-018-31897-2}, issn = {4159801831897}, year = {2018}, date = {2018-01-01}, journal = {Scientific Reports}, volume = {8}, number = {1}, pages = {1-9}, abstract = {Fluorescent base analogues (FBAs) have emerged as a powerful class of molecular reporters of location and environment for nucleic acids. In our overall mission to develop bright and useful FBAs for all natural nucleobases, herein we describe the synthesis and thorough characterization of bicyclic thymidine (bT), both as a monomer and when incorporated into DNA. We have developed a robust synthetic route for the preparation of the bT DNA monomer and the corresponding protected phosphoramidite for solid-phase DNA synthesis. The bT deoxyribonucleoside has a brightness value of 790 M-1cm-1 in water, which is comparable or higher than most fluorescent thymine analogues reported. When incorporated into DNA, bT pairs selectively with adenine without perturbing the B-form structure, keeping the melting thermodynamics of the B-form duplex DNA virtually unchanged. As for most fluorescent base analogues, the emission of bT is reduced inside DNA (4.5- and 13-fold in single- and double-stranded DNA, respectively). Overall, these properties make bT an interesting thymine analogue for studying DNA and an excellent starting point for the development of brighter bT derivatives.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Fluorescent base analogues (FBAs) have emerged as a powerful class of molecular reporters of location and environment for nucleic acids. In our overall mission to develop bright and useful FBAs for all natural nucleobases, herein we describe the synthesis and thorough characterization of bicyclic thymidine (bT), both as a monomer and when incorporated into DNA. We have developed a robust synthetic route for the preparation of the bT DNA monomer and the corresponding protected phosphoramidite for solid-phase DNA synthesis. The bT deoxyribonucleoside has a brightness value of 790 M-1cm-1 in water, which is comparable or higher than most fluorescent thymine analogues reported. When incorporated into DNA, bT pairs selectively with adenine without perturbing the B-form structure, keeping the melting thermodynamics of the B-form duplex DNA virtually unchanged. As for most fluorescent base analogues, the emission of bT is reduced inside DNA (4.5- and 13-fold in single- and double-stranded DNA, respectively). Overall, these properties make bT an interesting thymine analogue for studying DNA and an excellent starting point for the development of brighter bT derivatives. |
Taming Nickel-Catalyzed Suzuki-Miyaura Coupling: A Mechanistic Focus on Boron-to-Nickel Transmetalation Article de journal P -A Payard; L A Perego; I Ciofini; L Grimaud ACS Catalysis, 8 (6), p. 4812–4823, 2018. @article{Payard:2018a, title = {Taming Nickel-Catalyzed Suzuki-Miyaura Coupling: A Mechanistic Focus on Boron-to-Nickel Transmetalation}, author = {P -A Payard and L A Perego and I Ciofini and L Grimaud}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85046455355&doi=10.1021%2facscatal.8b00933&partnerID=40&md5=caf0fb0bb4baa9b47d85ebce2e2b0045}, doi = {10.1021/acscatal.8b00933}, year = {2018}, date = {2018-01-01}, journal = {ACS Catalysis}, volume = {8}, number = {6}, pages = {4812--4823}, abstract = {The mechanism of boron-to-nickel transmetalation, the key step of the nickel-catalyzed Suzuki-Miyaura (S-M) coupling, was examined both experimentally and theoretically. Dinuclear μ-hydroxo-bridged complexes formed by reaction of trans-[ArNi(PR3)2X] with hydroxide are not directly involved in transmetalation, but they rather act as a resting state for the catalyst. The base/boronic acid ratio is the crucial parameter, as it modulates the extent of formation of these dinuclear species and thus tunes the catalytic activity. These findings explain some limitations encountered in practical applications of nickel-catalyzed S-M couplings and suggest how to tailor the experimental conditions in order to overcome these difficulties. © 2018 American Chemical Society.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The mechanism of boron-to-nickel transmetalation, the key step of the nickel-catalyzed Suzuki-Miyaura (S-M) coupling, was examined both experimentally and theoretically. Dinuclear μ-hydroxo-bridged complexes formed by reaction of trans-[ArNi(PR3)2X] with hydroxide are not directly involved in transmetalation, but they rather act as a resting state for the catalyst. The base/boronic acid ratio is the crucial parameter, as it modulates the extent of formation of these dinuclear species and thus tunes the catalytic activity. These findings explain some limitations encountered in practical applications of nickel-catalyzed S-M couplings and suggest how to tailor the experimental conditions in order to overcome these difficulties. © 2018 American Chemical Society. |
TiCl 4 -Mediated Synthesis of 3,4-Hetero-Disubstituted Isocoumarins by Means of Isocyanide Insertion Reactions Article de journal S Ponra; A Nyadanu; S Maurin; L El Kaïm; L Grimaud; M R Vitale Synthesis (Germany), 50 (6), p. 1331–1342, 2018. @article{Ponra:2018, title = {TiCl 4 -Mediated Synthesis of 3,4-Hetero-Disubstituted Isocoumarins by Means of Isocyanide Insertion Reactions}, author = {S Ponra and A Nyadanu and S Maurin and L El Ka\"{i}m and L Grimaud and M R Vitale}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85038371806&doi=10.1055%2fs-0036-1591733&partnerID=40&md5=baf4a0e29e4d642c2aeebdd1b35bb541}, doi = {10.1055/s-0036-1591733}, year = {2018}, date = {2018-01-01}, journal = {Synthesis (Germany)}, volume = {50}, number = {6}, pages = {1331--1342}, abstract = {The isocyanide insertion into sulfanyl-phthalides under Lewis acid conditions is reported with full details. This sequential three-component reaction affords a new straightforward and highly convenient method for the preparation of 3-amino-4-sulfanyl isocoumarins, the potential of which is still unexplored.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The isocyanide insertion into sulfanyl-phthalides under Lewis acid conditions is reported with full details. This sequential three-component reaction affords a new straightforward and highly convenient method for the preparation of 3-amino-4-sulfanyl isocoumarins, the potential of which is still unexplored. |
A novel diarylethene-based photoswitchable chelator for reversible release and capture of Ca2+ in aqueous media Article de journal N Dozova; G Pousse; B Barnych; J -M Mallet; J Cossy; B Valeur; P Plaza Journal of Photochemistry and Photobiology A: Chemistry, 360 , p. 181–187, 2018. @article{Dozova:2018, title = {A novel diarylethene-based photoswitchable chelator for reversible release and capture of Ca2+ in aqueous media}, author = {N Dozova and G Pousse and B Barnych and J -M Mallet and J Cossy and B Valeur and P Plaza}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85046375200&doi=10.1016%2fj.jphotochem.2018.04.029&partnerID=40&md5=acfff9bc55e2d0bb41580e84374018fc}, doi = {10.1016/j.jphotochem.2018.04.029}, year = {2018}, date = {2018-01-01}, journal = {Journal of Photochemistry and Photobiology A: Chemistry}, volume = {360}, pages = {181--187}, abstract = {The synthesis and characterisation of a novel Reversibly Photoswitchable Chelator (RPC) of calcium ions, designed as a stepping stone towards producing pulses of calcium concentration in an aqueous environment, is reported. This RPC is constituted of a photochromic diarylethene core connected on one side to a BAPTA (1,2-bis(2-aminophenoxy)ethane-N,N,N’,N’-tetraacetic acid) calcium chelator and, on the other side, to an electron-withdrawing group. The operation principle consists in photoswitching on and off an intramolecular charge transfer between one nitrogen atom of the BAPTA moiety and the electron-withdrawing group, thereby modulating the chelating affinity of BAPTA for calcium ions. Solubility of the compound in a partially aqueous solvent was achieved by grafting a short PEG (polyethylene glycol) tail to the electron-withdrawing group. A reduction of the affinity for calcium ions upon photoswitching by a factor of 3\textendash4, in the hundred nM range of dissociation constant, is reported and constitutes a proof of concept of this type of RPC. © 2018 Elsevier B.V.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The synthesis and characterisation of a novel Reversibly Photoswitchable Chelator (RPC) of calcium ions, designed as a stepping stone towards producing pulses of calcium concentration in an aqueous environment, is reported. This RPC is constituted of a photochromic diarylethene core connected on one side to a BAPTA (1,2-bis(2-aminophenoxy)ethane-N,N,N’,N’-tetraacetic acid) calcium chelator and, on the other side, to an electron-withdrawing group. The operation principle consists in photoswitching on and off an intramolecular charge transfer between one nitrogen atom of the BAPTA moiety and the electron-withdrawing group, thereby modulating the chelating affinity of BAPTA for calcium ions. Solubility of the compound in a partially aqueous solvent was achieved by grafting a short PEG (polyethylene glycol) tail to the electron-withdrawing group. A reduction of the affinity for calcium ions upon photoswitching by a factor of 3–4, in the hundred nM range of dissociation constant, is reported and constitutes a proof of concept of this type of RPC. © 2018 Elsevier B.V. |
Evidence for a Cooperative Mechanism Involving Two Palladium(0) Centers in the Oxidative Addition of Iodoarenes Article de journal L A Perego; P -A Payard; B Haddou; I Ciofini; L Grimaud Chemistry - A European Journal, 24 (9), p. 2192–2199, 2018. @article{Perego:2018, title = {Evidence for a Cooperative Mechanism Involving Two Palladium(0) Centers in the Oxidative Addition of Iodoarenes}, author = {L A Perego and P -A Payard and B Haddou and I Ciofini and L Grimaud}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85040731231&doi=10.1002%2fchem.201704899&partnerID=40&md5=04a20da1a343e3ea2009facbdde3fbd9}, doi = {10.1002/chem.201704899}, year = {2018}, date = {2018-01-01}, journal = {Chemistry - A European Journal}, volume = {24}, number = {9}, pages = {2192--2199}, abstract = {Oxidative addition of iodoarenes (ArI) to Pd0 ligated by 1-methyl-1H-imidazole (mim) in polar solvents leads to cationic arylpalladium(II) complexes [ArPd(mim)3]+. Kinetic analyses evidence that this reaction is second order with respect to the concentration of Pd0, and a mechanism involving the cooperative intervention of two Pd0 centers has been postulated to explain this finding. This unusual behavior is also observed with other nitrogen-containing ligands and it is general for iodobenzenes substituted with electron-donating or weakly electron-withdrawing groups. In contrast, bromoarenes and electron-poor iodoarenes display first-order kinetics with respect to Pd0. Theoretical calculations performed at the density functional theory (DFT) level suggest the existence of mim-ligated ArI-Pd0 complexes, in which the iodoarene is bound to the metal in a halogen-bond-like fashion. Coordination weakens the C−I bond and facilitates the oxidative insertion of another Pd0 center across this C−I bond. This conceptually novel mechanism, involving the cooperative participation of two distinct metal centers, allows a full explanation of the experimentally observed kinetics. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim}, keywords = {}, pubstate = {published}, tppubtype = {article} } Oxidative addition of iodoarenes (ArI) to Pd0 ligated by 1-methyl-1H-imidazole (mim) in polar solvents leads to cationic arylpalladium(II) complexes [ArPd(mim)3]+. Kinetic analyses evidence that this reaction is second order with respect to the concentration of Pd0, and a mechanism involving the cooperative intervention of two Pd0 centers has been postulated to explain this finding. This unusual behavior is also observed with other nitrogen-containing ligands and it is general for iodobenzenes substituted with electron-donating or weakly electron-withdrawing groups. In contrast, bromoarenes and electron-poor iodoarenes display first-order kinetics with respect to Pd0. Theoretical calculations performed at the density functional theory (DFT) level suggest the existence of mim-ligated ArI-Pd0 complexes, in which the iodoarene is bound to the metal in a halogen-bond-like fashion. Coordination weakens the C−I bond and facilitates the oxidative insertion of another Pd0 center across this C−I bond. This conceptually novel mechanism, involving the cooperative participation of two distinct metal centers, allows a full explanation of the experimentally observed kinetics. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim |
Inter-kingdom effect on epithelial cells of the N-Acyl homoserine lactone 3-oxo-C12:2, a major quorum-sensing molecule from gut microbiota Article de journal C Landman; J -P Grill; J -M Mallet; P Marteau; L Humbert; E L Balc’h; M -A Maubert; K Perez; W Chaara; L Brot; L Beaugerie; H Sokol; S Thenet; D Rainteau; P Seksik; E Quévrain PLoS ONE, 13 (8), 2018. @article{Landman:2018, title = {Inter-kingdom effect on epithelial cells of the N-Acyl homoserine lactone 3-oxo-C12:2, a major quorum-sensing molecule from gut microbiota}, author = {C Landman and J -P Grill and J -M Mallet and P Marteau and L Humbert and E L Balc’h and M -A Maubert and K Perez and W Chaara and L Brot and L Beaugerie and H Sokol and S Thenet and D Rainteau and P Seksik and E Qu\'{e}vrain}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85052807116&doi=10.1371%2fjournal.pone.0202587&partnerID=40&md5=ff949e3ec9730a2a172169cfa8e56815}, doi = {10.1371/journal.pone.0202587}, year = {2018}, date = {2018-01-01}, journal = {PLoS ONE}, volume = {13}, number = {8}, abstract = {Background and aims N-acyl homoserine lactones (AHLs), which are autoinducer quorum-sensing molecules involved in the bacterial communication network, also interact with eukaryotic cells. Searching for these molecules in the context of inflammatory bowel disease (IBD) is appealing. The aims of our study were to look for AHL molecules in faecal samples from healthy subjects (HS) and IBD patients to correlate AHL profiles with the microbiome and investigate the effect of AHLs of interest on epithelial cells. Methods Using mass spectrometry, we characterised AHL profiles in faecal samples from HS (n = 26) and IBD patients in remission (n = 24) and in flare (n = 25) and correlated the presence of AHLs of interest with gut microbiota composition obtained by real-time qPCR and 16S sequencing. We synthesised AHLs of interest to test the inflammatory response after IL1β stimulation and paracellular permeability on Caco-2 cells. Results We observed 14 different AHLs, among which one was prominent. This AHL corresponded to 3-oxo-C12:2 and was found significantly less frequently in IBD patients in flare (16%) and in remission (37.5%) versus HS (65.4%) (p = 0.001). The presence of 3-oxo-C12:2 was associated with significantly higher counts of Firmicutes, especially Faecalbacterium prausnitzii, and lower counts of Escherichia coli. In vitro, 3-oxo-C12:2 exerted an anti-inflammatory effect on Caco-2 cells. Interestingly, although 3-oxo-C12, the well-known AHL from Pseudomonas aeruginosa, increased paracellular permeability, 3-oxo-C12:2 did not. Conclusions We identified AHLs in the human gut microbiota and discovered a new and prominent AHL, 3-oxo-C12:2, which correlates with normobiosis and exerts a protective effect on gut epithelial cells. © 2018 Landman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background and aims N-acyl homoserine lactones (AHLs), which are autoinducer quorum-sensing molecules involved in the bacterial communication network, also interact with eukaryotic cells. Searching for these molecules in the context of inflammatory bowel disease (IBD) is appealing. The aims of our study were to look for AHL molecules in faecal samples from healthy subjects (HS) and IBD patients to correlate AHL profiles with the microbiome and investigate the effect of AHLs of interest on epithelial cells. Methods Using mass spectrometry, we characterised AHL profiles in faecal samples from HS (n = 26) and IBD patients in remission (n = 24) and in flare (n = 25) and correlated the presence of AHLs of interest with gut microbiota composition obtained by real-time qPCR and 16S sequencing. We synthesised AHLs of interest to test the inflammatory response after IL1β stimulation and paracellular permeability on Caco-2 cells. Results We observed 14 different AHLs, among which one was prominent. This AHL corresponded to 3-oxo-C12:2 and was found significantly less frequently in IBD patients in flare (16%) and in remission (37.5%) versus HS (65.4%) (p = 0.001). The presence of 3-oxo-C12:2 was associated with significantly higher counts of Firmicutes, especially Faecalbacterium prausnitzii, and lower counts of Escherichia coli. In vitro, 3-oxo-C12:2 exerted an anti-inflammatory effect on Caco-2 cells. Interestingly, although 3-oxo-C12, the well-known AHL from Pseudomonas aeruginosa, increased paracellular permeability, 3-oxo-C12:2 did not. Conclusions We identified AHLs in the human gut microbiota and discovered a new and prominent AHL, 3-oxo-C12:2, which correlates with normobiosis and exerts a protective effect on gut epithelial cells. © 2018 Landman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
4-Aminopyrimidine libraries from the Ugi-Smiles reaction of thiouracil Article de journal M A Sidhoum; L El Kaïm; L Grimaud Tetrahedron, 74 (38), p. 5222–5231, 2018. @article{Sidhoum:2018, title = {4-Aminopyrimidine libraries from the Ugi-Smiles reaction of thiouracil}, author = {M A Sidhoum and L El Ka\"{i}m and L Grimaud}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85046157652&doi=10.1016%2fj.tet.2018.04.058&partnerID=40&md5=fe5adb80c898e954107e7970320ea457}, doi = {10.1016/j.tet.2018.04.058}, year = {2018}, date = {2018-01-01}, journal = {Tetrahedron}, volume = {74}, number = {38}, pages = {5222--5231}, abstract = {The Ugi-Smiles reaction of S-benzyl thiouracil have been exploited in several three-step sequences for the preparation of aminopyrimidine libraries with high diversity. After the 4-component coupling, oxidation of the thioether to sulfone is followed by displacement of the latter by various carbon-centered nucleophiles (cyanide, malonate, boronic acids) or amines. The efficiency of the whole sequence was further demonstrated with one-pot procedures. © 2018}, keywords = {}, pubstate = {published}, tppubtype = {article} } The Ugi-Smiles reaction of S-benzyl thiouracil have been exploited in several three-step sequences for the preparation of aminopyrimidine libraries with high diversity. After the 4-component coupling, oxidation of the thioether to sulfone is followed by displacement of the latter by various carbon-centered nucleophiles (cyanide, malonate, boronic acids) or amines. The efficiency of the whole sequence was further demonstrated with one-pot procedures. © 2018 |