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.
2017 |
R de Oliveira; M Durand; L Challier; P Messina; J M Swiecicki; M Di Pisa; G Chassaing; S Lavielle; O Buriez; E Labbé Journal of Electroanalytical Chemistry, 788 , p. 225–231, 2017. @article{deOliveira:2017, title = {Electrochemical quenching of the fluorescence produced by NBD-labelled cell penetrating peptides: A contribution to the study of their internalization in large unilamellar vesicles}, author = {R de Oliveira and M Durand and L Challier and P Messina and J M Swiecicki and M Di Pisa and G Chassaing and S Lavielle and O Buriez and E Labb\'{e}}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85013176758&doi=10.1016%2fj.jelechem.2017.02.006&partnerID=40&md5=725e8c07b1f4090ecf4f2ceabb57e6f7}, doi = {10.1016/j.jelechem.2017.02.006}, year = {2017}, date = {2017-01-01}, journal = {Journal of Electroanalytical Chemistry}, volume = {788}, pages = {225--231}, abstract = {This work investigates the implementation of a simple and versatile electrochemical setup aimed at achieving a fast and complete fluorescence extinction of NBD-labelled (NBD = 7-nitrobenz-2-oxa-1,3-diazole) cell penetrating peptides contained in 2\textendash5 cm3 samples containing phosphate buffer + large unilamellar vesicles. The quenching is obtained through a reductive electrolysis in a 2-compartment cell homebuilt from disposable plastic labware, which remains inert towards the adsorption of both peptides and lipid vesicles. Considering the micromolar concentration of NBD-tagged peptides, the main electrochemical reaction observed is hydrogen evolution, NBD reduction representing a small fraction of the cathodic current/charge engaged. The electrolysis conditions are discussed with respect to the nature of the reduction products formed, the integrity of large unilamellar vesicles and phosphate buffering properties. This electrochemical method is compared to the traditional chemical dithionite quenching of NBD and tested to monitor the internalization of cell penetrating peptides in large unilamellar vesicles. © 2017 Elsevier B.V.}, keywords = {}, pubstate = {published}, tppubtype = {article} } This work investigates the implementation of a simple and versatile electrochemical setup aimed at achieving a fast and complete fluorescence extinction of NBD-labelled (NBD = 7-nitrobenz-2-oxa-1,3-diazole) cell penetrating peptides contained in 2–5 cm3 samples containing phosphate buffer + large unilamellar vesicles. The quenching is obtained through a reductive electrolysis in a 2-compartment cell homebuilt from disposable plastic labware, which remains inert towards the adsorption of both peptides and lipid vesicles. Considering the micromolar concentration of NBD-tagged peptides, the main electrochemical reaction observed is hydrogen evolution, NBD reduction representing a small fraction of the cathodic current/charge engaged. The electrolysis conditions are discussed with respect to the nature of the reduction products formed, the integrity of large unilamellar vesicles and phosphate buffering properties. This electrochemical method is compared to the traditional chemical dithionite quenching of NBD and tested to monitor the internalization of cell penetrating peptides in large unilamellar vesicles. © 2017 Elsevier B.V. |
Identification of the Tau phosphorylation pattern that drives its aggregation Article de journal C Despres; C Byrne; H Qi; F -X Cantrelle; I Huvent; B Chambraud; E -E Baulieu; Y Jacquot; I Landrieu; G Lippens; C Smet-Nocca Proceedings of the National Academy of Sciences of the United States of America, 114 (34), p. 9080–9085, 2017. @article{Despres:2017, title = {Identification of the Tau phosphorylation pattern that drives its aggregation}, author = {C Despres and C Byrne and H Qi and F -X Cantrelle and I Huvent and B Chambraud and E -E Baulieu and Y Jacquot and I Landrieu and G Lippens and C Smet-Nocca}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85027866366&doi=10.1073%2fpnas.1708448114&partnerID=40&md5=54e7f2c753bbd1b2171962fa9cf74fde}, doi = {10.1073/pnas.1708448114}, year = {2017}, date = {2017-01-01}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {114}, number = {34}, pages = {9080--9085}, abstract = {Determining the functional relationship between Tau phosphorylation and aggregation has proven a challenge owing to the multiple potential phosphorylation sites and their clustering in the Tau sequence. We use here in vitro kinase assays combined with NMR spectroscopy as an analytical tool to generate well-characterized phosphorylated Tau samples and show that the combined phosphorylation at the Ser202/Thr205/Ser208 sites, together with absence of phosphorylation at the Ser262 site, yields a Tau sample that readily forms fibers, as observed by thioflavin T fluorescence and electron microscopy. On the basis of conformational analysis of synthetic phosphorylated peptides, we show that aggregation of the samples correlates with destabilization of the turn-like structure defined by phosphorylation of Ser202/Thr205. © 2017, National Academy of Sciences. All rights reserved.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Determining the functional relationship between Tau phosphorylation and aggregation has proven a challenge owing to the multiple potential phosphorylation sites and their clustering in the Tau sequence. We use here in vitro kinase assays combined with NMR spectroscopy as an analytical tool to generate well-characterized phosphorylated Tau samples and show that the combined phosphorylation at the Ser202/Thr205/Ser208 sites, together with absence of phosphorylation at the Ser262 site, yields a Tau sample that readily forms fibers, as observed by thioflavin T fluorescence and electron microscopy. On the basis of conformational analysis of synthetic phosphorylated peptides, we show that aggregation of the samples correlates with destabilization of the turn-like structure defined by phosphorylation of Ser202/Thr205. © 2017, National Academy of Sciences. All rights reserved. |
ERα dimerization: a key factor for the weak estrogenic activity of an ERα modulator unable to compete with estradiol in binding assays Article de journal G Leclercq; I Laïos; C Elie-Caille; D Leiber; G Laurent; E Lesniewska; Z Tanfin; Y Jacquot Journal of Receptors and Signal Transduction, 37 (2), p. 149–166, 2017. @article{Leclercq:2017, title = {ERα dimerization: a key factor for the weak estrogenic activity of an ERα modulator unable to compete with estradiol in binding assays}, author = {G Leclercq and I La\"{i}os and C Elie-Caille and D Leiber and G Laurent and E Lesniewska and Z Tanfin and Y Jacquot}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84978160581&doi=10.1080%2f10799893.2016.1203940&partnerID=40&md5=5ed36d16cd7bed348ed361de9fc2db49}, doi = {10.1080/10799893.2016.1203940}, year = {2017}, date = {2017-01-01}, journal = {Journal of Receptors and Signal Transduction}, volume = {37}, number = {2}, pages = {149--166}, abstract = {Estrothiazine (ESTZ) is a weak estrogen sharing structural similarities with coumestrol. ESTZ failed to compete with [3H]17β-estradiol ([3H]17β-E2) for binding to the estrogen receptor α (ERα), questioning its ability to interact with the receptor. However, detection by atomic force spectroscopy (AFS) of an ESTZ-induced ERα dimerization has eliminated any remaining doubts. The effect of the compound on the proliferation of ERα-positive and negative breast cancer cells confirmed the requirement of the receptor. The efficiency of ESTZ in MCF-7 cells was weak without any potency to modify the proliferation profile of estradiol and coumestrol. Growth enhancement was associated with a proteasomal degradation of ERα without substantial recruitment of LxxLL coactivators. This may be related to an unusual delay between the acquisition by the receptor of an ERE-binding capacity and the subsequent estrogen-dependent transcription. A complementary ability to enhance TPA-induced AP-1 transcription was observed, even at concentrations insufficient to activate the ERα, suggesting a partly independent mechanism. ESTZ also rapidly and transiently activated ERK1/2 likely through membrane estrogenic pathways provoking a reorganization of the actin network. Finally, the systematic absence of biological responses with an ESTZ derivative unable to induce ERα dimerization stresses the importance of this step in the action of the compound, as reported for conventional estrogens. In view of the existence of many other ERα modulators (endocrine disruptors such as, for example, pesticides, environmental contaminants or phytoestrogens) with extremely weak or similar apparent lack of binding ability, our work may appear as pilot investigation for assessing their mechanism of action. © 2016 Informa UK Limited, trading as Taylor & Francis Group.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Estrothiazine (ESTZ) is a weak estrogen sharing structural similarities with coumestrol. ESTZ failed to compete with [3H]17β-estradiol ([3H]17β-E2) for binding to the estrogen receptor α (ERα), questioning its ability to interact with the receptor. However, detection by atomic force spectroscopy (AFS) of an ESTZ-induced ERα dimerization has eliminated any remaining doubts. The effect of the compound on the proliferation of ERα-positive and negative breast cancer cells confirmed the requirement of the receptor. The efficiency of ESTZ in MCF-7 cells was weak without any potency to modify the proliferation profile of estradiol and coumestrol. Growth enhancement was associated with a proteasomal degradation of ERα without substantial recruitment of LxxLL coactivators. This may be related to an unusual delay between the acquisition by the receptor of an ERE-binding capacity and the subsequent estrogen-dependent transcription. A complementary ability to enhance TPA-induced AP-1 transcription was observed, even at concentrations insufficient to activate the ERα, suggesting a partly independent mechanism. ESTZ also rapidly and transiently activated ERK1/2 likely through membrane estrogenic pathways provoking a reorganization of the actin network. Finally, the systematic absence of biological responses with an ESTZ derivative unable to induce ERα dimerization stresses the importance of this step in the action of the compound, as reported for conventional estrogens. In view of the existence of many other ERα modulators (endocrine disruptors such as, for example, pesticides, environmental contaminants or phytoestrogens) with extremely weak or similar apparent lack of binding ability, our work may appear as pilot investigation for assessing their mechanism of action. © 2016 Informa UK Limited, trading as Taylor & Francis Group. |
Y Jacquot; D Spaggiari; J Schappler; E Lesniewska; S Rudaz; G Leclercq European Journal of Pharmaceutical Sciences, 109 , p. 169–181, 2017. @article{Jacquot:2017, title = {ERE-dependent transcription and cell proliferation: Independency of these two processes mediated by the introduction of a sulfone function into the weak estrogen estrothiazine}, author = {Y Jacquot and D Spaggiari and J Schappler and E Lesniewska and S Rudaz and G Leclercq}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85028007094&doi=10.1016%2fj.ejps.2017.07.026&partnerID=40&md5=f0d8a84c9a0461377a0a813ab7bd745c}, doi = {10.1016/j.ejps.2017.07.026}, year = {2017}, date = {2017-01-01}, journal = {European Journal of Pharmaceutical Sciences}, volume = {109}, pages = {169--181}, abstract = {The synthetic coumestrol derivative 6,12-dihydro-3-methoxy-1-benzopyrano[3,4-b][1,4]benzothiazin-6-one (estrothiazine, ESTZ) has been identified as a weak estrogen receptor α (ERα) ligand unable to compete with tritiated estradiol. The biological activity of this compound, supported by a methoxy group in position 3, seems mainly to result from its capacity to activate ERα dimerization without any participation of coactivators. In support of this view and referring to conventional estrogens, an ESTZ metabolism study conducted with hepatic human microsomes failed to provide any argument in favour of an estrogenic activity dependent on a metabolic conversion of the compound into hydroxylated metabolites with strong receptor activation ability. Interestingly, we failed to detect any oxidation of the sulfur atom of the compound. In the light of pharmacological literature data concerning sulfonylation, we assessed ERα-mediated activities generated by two sulfonylated ESTZ derivatives in which the methoxy group that plays a key role in its mechanism of action was maintained or removed. Sulfonylated ESTZ, even in its demethoxylated form, induced ERE-mediated transcriptions in MCF-7 breast cancer cells, without affecting the ERα turnover rate. In contrast to ESTZ, this compound failed to enhance the proliferation of ERα-positive breast cancer cells, suggesting that its sulfone function confers upon the receptor a capacity to elicit some of the known characteristics associated with estrogenic responses. Moreover, we demonstrated that this sulfone may contribute to ERα dimerization without any requirement of the methoxy group. Nevertheless, it seems to cooperate with this group, as reflected by a weak ability of the sulfonylated form of ESTZ to compete with tritiated estradiol for ERα-binding. Assessment of the docking of this compound within the ligand-binding domain of the receptor by molecular dynamics provided an explanation for this observation since the sulfone is engulfed in a small hydrophobic pocket involving the residues Leu-346, Leu-349, Ala-350 and Leu-384, also known to recruit coactivators. This work not only reports the sulfone functional group as a pharmacophore for estrogenic activity, but also opens new perspectives for the development of estrogenic molecules with therapeutic purpose and devoid of proliferative side effects. © 2017 Elsevier B.V.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The synthetic coumestrol derivative 6,12-dihydro-3-methoxy-1-benzopyrano[3,4-b][1,4]benzothiazin-6-one (estrothiazine, ESTZ) has been identified as a weak estrogen receptor α (ERα) ligand unable to compete with tritiated estradiol. The biological activity of this compound, supported by a methoxy group in position 3, seems mainly to result from its capacity to activate ERα dimerization without any participation of coactivators. In support of this view and referring to conventional estrogens, an ESTZ metabolism study conducted with hepatic human microsomes failed to provide any argument in favour of an estrogenic activity dependent on a metabolic conversion of the compound into hydroxylated metabolites with strong receptor activation ability. Interestingly, we failed to detect any oxidation of the sulfur atom of the compound. In the light of pharmacological literature data concerning sulfonylation, we assessed ERα-mediated activities generated by two sulfonylated ESTZ derivatives in which the methoxy group that plays a key role in its mechanism of action was maintained or removed. Sulfonylated ESTZ, even in its demethoxylated form, induced ERE-mediated transcriptions in MCF-7 breast cancer cells, without affecting the ERα turnover rate. In contrast to ESTZ, this compound failed to enhance the proliferation of ERα-positive breast cancer cells, suggesting that its sulfone function confers upon the receptor a capacity to elicit some of the known characteristics associated with estrogenic responses. Moreover, we demonstrated that this sulfone may contribute to ERα dimerization without any requirement of the methoxy group. Nevertheless, it seems to cooperate with this group, as reflected by a weak ability of the sulfonylated form of ESTZ to compete with tritiated estradiol for ERα-binding. Assessment of the docking of this compound within the ligand-binding domain of the receptor by molecular dynamics provided an explanation for this observation since the sulfone is engulfed in a small hydrophobic pocket involving the residues Leu-346, Leu-349, Ala-350 and Leu-384, also known to recruit coactivators. This work not only reports the sulfone functional group as a pharmacophore for estrogenic activity, but also opens new perspectives for the development of estrogenic molecules with therapeutic purpose and devoid of proliferative side effects. © 2017 Elsevier B.V. |
Exploiting Benzophenone Photoreactivity To Probe the Phospholipid Environment and Insertion Depth of the Cell-Penetrating Peptide Penetratin in Model Membranes Article de journal C -Y Jiao; E Sachon; I D Alves; G Chassaing; G Bolbach; S Sagan Angewandte Chemie - International Edition, 56 (28), p. 8226–8230, 2017. @article{Jiao:2017, title = {Exploiting Benzophenone Photoreactivity To Probe the Phospholipid Environment and Insertion Depth of the Cell-Penetrating Peptide Penetratin in Model Membranes}, author = {C -Y Jiao and E Sachon and I D Alves and G Chassaing and G Bolbach and S Sagan}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85021264790&doi=10.1002%2fanie.201703465&partnerID=40&md5=27efd27206b0847481f97a36b451b7a1}, doi = {10.1002/anie.201703465}, year = {2017}, date = {2017-01-01}, journal = {Angewandte Chemie - International Edition}, volume = {56}, number = {28}, pages = {8226--8230}, abstract = {Penetratin (RQIKIWFQNRRMKWKK) enters cells by different mechanisms, including membrane translocation, thus implying that the peptide interacts with the lipid bilayer. Penetratin also crosses the membrane of artificial vesicles, depending on their phospholipid content. To evaluate the phospholipid preference of penetratin, as the first step of translocation, we exploited the benzophenone triplet kinetics of hydrogen abstraction, which is slower for secondary than for allylic hydrogen atoms. By using multilamellar vesicles of varying phospholipid content, we identified and characterized the cross-linked products by MALDI-TOF mass spectrometry. Penetratin showed a preference for negatively charged (vs. zwitterionic) polar heads, and for unsaturated (vs. saturated) and short (vs. long) saturated phospholipids. Our study highlights the potential of using benzophenone to probe the environment and insertion depth of membranotropic peptides in membranes. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim}, keywords = {}, pubstate = {published}, tppubtype = {article} } Penetratin (RQIKIWFQNRRMKWKK) enters cells by different mechanisms, including membrane translocation, thus implying that the peptide interacts with the lipid bilayer. Penetratin also crosses the membrane of artificial vesicles, depending on their phospholipid content. To evaluate the phospholipid preference of penetratin, as the first step of translocation, we exploited the benzophenone triplet kinetics of hydrogen abstraction, which is slower for secondary than for allylic hydrogen atoms. By using multilamellar vesicles of varying phospholipid content, we identified and characterized the cross-linked products by MALDI-TOF mass spectrometry. Penetratin showed a preference for negatively charged (vs. zwitterionic) polar heads, and for unsaturated (vs. saturated) and short (vs. long) saturated phospholipids. Our study highlights the potential of using benzophenone to probe the environment and insertion depth of membranotropic peptides in membranes. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim |
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. |
Structure and Dynamics of an Intrinsically Disordered Protein Region That Partially Folds upon Binding by Chemical-Exchange NMR Article de journal C Charlier; G Bouvignies; P Pelupessy; A Walrant; R Marquant; M Kozlov; P De Ioannes; N Bolik-Coulon; S Sagan; P Cortes; A K Aggarwal; L Carlier; F Ferrage Journal of the American Chemical Society, 139 (35), p. 12219–12227, 2017. @article{Charlier:2017, title = {Structure and Dynamics of an Intrinsically Disordered Protein Region That Partially Folds upon Binding by Chemical-Exchange NMR}, author = {C Charlier and G Bouvignies and P Pelupessy and A Walrant and R Marquant and M Kozlov and P De Ioannes and N Bolik-Coulon and S Sagan and P Cortes and A K Aggarwal and L Carlier and F Ferrage}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85028941202&doi=10.1021%2fjacs.7b05823&partnerID=40&md5=ce8846a9b03d31576ec301899a2c40f1}, doi = {10.1021/jacs.7b05823}, year = {2017}, date = {2017-01-01}, journal = {Journal of the American Chemical Society}, volume = {139}, number = {35}, pages = {12219--12227}, abstract = {Many intrinsically disordered proteins (IDPs) and protein regions (IDRs) engage in transient, yet specific, interactions with a variety of protein partners. Often, if not always, interactions with a protein partner lead to partial folding of the IDR. Characterizing the conformational space of such complexes is challenging: in solution-state NMR, signals of the IDR in the interacting region become broad, weak, and often invisible, while X-ray crystallography only provides information on fully ordered regions. There is thus a need for a simple method to characterize both fully and partially ordered regions in the bound state of IDPs. Here, we introduce an approach based on monitoring chemical exchange by NMR to investigate the state of an IDR that folds upon binding through the observation of the free state of the protein. Structural constraints for the bound state are obtained from chemical shifts, and site-specific dynamics of the bound state are characterized by relaxation rates. The conformation of the interacting part of the IDR was determined and subsequently docked onto the structure of the folded partner. We apply the method to investigate the interaction between the disordered C-terminal region of Artemis and the DNA binding domain of Ligase IV. We show that we can accurately reproduce the structure of the core of the complex determined by X-ray crystallography and identify a broader interface. The method is widely applicable to the biophysical investigation of complexes of disordered proteins and folded proteins. © 2017 American Chemical Society.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Many intrinsically disordered proteins (IDPs) and protein regions (IDRs) engage in transient, yet specific, interactions with a variety of protein partners. Often, if not always, interactions with a protein partner lead to partial folding of the IDR. Characterizing the conformational space of such complexes is challenging: in solution-state NMR, signals of the IDR in the interacting region become broad, weak, and often invisible, while X-ray crystallography only provides information on fully ordered regions. There is thus a need for a simple method to characterize both fully and partially ordered regions in the bound state of IDPs. Here, we introduce an approach based on monitoring chemical exchange by NMR to investigate the state of an IDR that folds upon binding through the observation of the free state of the protein. Structural constraints for the bound state are obtained from chemical shifts, and site-specific dynamics of the bound state are characterized by relaxation rates. The conformation of the interacting part of the IDR was determined and subsequently docked onto the structure of the folded partner. We apply the method to investigate the interaction between the disordered C-terminal region of Artemis and the DNA binding domain of Ligase IV. We show that we can accurately reproduce the structure of the core of the complex determined by X-ray crystallography and identify a broader interface. The method is widely applicable to the biophysical investigation of complexes of disordered proteins and folded proteins. © 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. |
2016 |
Studying Z-DNA and B- to Z-DNA Transitions Using a Cytosine Analogue FRET-Pair Article de journal Blaise Dumat; Anders Foller Larsen; Marcus L Wilhelmsson Nucleic Acids Research, 44 (11), p. e101-e101, 2016. @article{Dumat:2016, title = {Studying Z-DNA and B- to Z-DNA Transitions Using a Cytosine Analogue FRET-Pair}, author = {Blaise Dumat and Anders Foller Larsen and Marcus L Wilhelmsson}, doi = {10.1093/nar/gkw114}, year = {2016}, date = {2016-06-01}, journal = {Nucleic Acids Research}, volume = {44}, number = {11}, pages = {e101-e101}, abstract = {Herein, we report on the use of a tricyclic cytosine FRET pair, incorporated into DNA with different base pair separations, to study Z-DNA and B-Z DNA junc-tions. With its position inside the DNA structure, the FRET pair responds to a B-to Z-DNA transi-tion with a distinct change in FRET efficiency for each donor/acceptor configuration allowing reliable structural probing. Moreover, we show how fluores-cence spectroscopy and our cytosine analogues can be used to determine rate constants for the B-to Z-DNA transition mechanism. The modified cytosines have little influence on the transition and the FRET pair is thus an easily implemented and virtually non-perturbing fluorescence tool to study Z-DNA. This nucleobase analogue FRET pair represents a valu-able addition to the limited number of fluorescence methods available to study Z-DNA and we suggest it will facilitate, for example, deciphering the B-to Z-DNA transition mechanism and investigating the interaction of DNA with Z-DNA binding proteins.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Herein, we report on the use of a tricyclic cytosine FRET pair, incorporated into DNA with different base pair separations, to study Z-DNA and B-Z DNA junc-tions. With its position inside the DNA structure, the FRET pair responds to a B-to Z-DNA transi-tion with a distinct change in FRET efficiency for each donor/acceptor configuration allowing reliable structural probing. Moreover, we show how fluores-cence spectroscopy and our cytosine analogues can be used to determine rate constants for the B-to Z-DNA transition mechanism. The modified cytosines have little influence on the transition and the FRET pair is thus an easily implemented and virtually non-perturbing fluorescence tool to study Z-DNA. This nucleobase analogue FRET pair represents a valu-able addition to the limited number of fluorescence methods available to study Z-DNA and we suggest it will facilitate, for example, deciphering the B-to Z-DNA transition mechanism and investigating the interaction of DNA with Z-DNA binding proteins. |
Candida albicans β-1,2 mannosyl transferase Bmt3: Preparation and evaluation of a β (1,2), α (1,2)-tetramannosyl fluorescent substrate Article de journal L Cattiaux; A Mée; M Pourcelot; G Sfihi-Loualia; T Hurtaux; E Maes; C Fradin; B Sendid; D Poulain; E Fabre; F Delplace; Y Guérardel; J -M Mallet Bioorganic and Medicinal Chemistry, 24 (6), p. 1362–1368, 2016. @article{Cattiaux:2016, title = {Candida albicans β-1,2 mannosyl transferase Bmt3: Preparation and evaluation of a β (1,2), α (1,2)-tetramannosyl fluorescent substrate}, author = {L Cattiaux and A M\'{e}e and M Pourcelot and G Sfihi-Loualia and T Hurtaux and E Maes and C Fradin and B Sendid and D Poulain and E Fabre and F Delplace and Y Gu\'{e}rardel and J -M Mallet}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84959017817&doi=10.1016%2fj.bmc.2016.02.008&partnerID=40&md5=e3851c9bd6b9f1934462c8735a0de331}, doi = {10.1016/j.bmc.2016.02.008}, year = {2016}, date = {2016-01-01}, journal = {Bioorganic and Medicinal Chemistry}, volume = {24}, number = {6}, pages = {1362--1368}, abstract = {We describe for the first time the chemical synthesis of a tetramannoside, containing both α (1 → 2) and β (1 → 2) linkages. Dodecylthio (lauryl) glycosides were prepared from odorless dodecyl thiol and used as donors for the glycosylation steps. This tetramannoside, was coupled to a mantyl group, and revealed to be a perfect substrate of β-mannosyltransferase Bmt3, confirming the proposed specificity and allowing the preparation of a pentamannoside sequence (β Man (1,2) β Man (1,2) α Man (1,2) α Man (1,2) α Man) usable as a novel substrate for further elongation studies. © 2016 Elsevier Ltd. All rights reserved.}, keywords = {}, pubstate = {published}, tppubtype = {article} } We describe for the first time the chemical synthesis of a tetramannoside, containing both α (1 → 2) and β (1 → 2) linkages. Dodecylthio (lauryl) glycosides were prepared from odorless dodecyl thiol and used as donors for the glycosylation steps. This tetramannoside, was coupled to a mantyl group, and revealed to be a perfect substrate of β-mannosyltransferase Bmt3, confirming the proposed specificity and allowing the preparation of a pentamannoside sequence (β Man (1,2) β Man (1,2) α Man (1,2) α Man (1,2) α Man) usable as a novel substrate for further elongation studies. © 2016 Elsevier Ltd. All rights reserved. |
Formation and investigation of 6-cysteinyl amino methylated β-cyclodextrin self-assembled monolayers Article de journal V Kolivoška; R Sokolová; J Kocábová; C Loukou; J -M Mallet; M Hromadová Monatshefte fur Chemie, 147 (1), p. 45–51, 2016. @article{Kolivoska:2016, title = {Formation and investigation of 6-cysteinyl amino methylated β-cyclodextrin self-assembled monolayers}, author = {V Kolivo\v{s}ka and R Sokolov\'{a} and J Koc\'{a}bov\'{a} and C Loukou and J -M Mallet and M Hromadov\'{a}}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84952863776&doi=10.1007%2fs00706-015-1609-2&partnerID=40&md5=001daecf5d1e75e217cdba44d4cc9f35}, doi = {10.1007/s00706-015-1609-2}, year = {2016}, date = {2016-01-01}, journal = {Monatshefte fur Chemie}, volume = {147}, number = {1}, pages = {45--51}, abstract = {6 -Cysteinyl amino methylated β-cyclodextrin was adsorbed on Au(111) as well as on mercury electrode. Scanning probe microscopy and electrochemical techniques confirmed that a chemisorbed self-assembled monolayer (SAM) of the β-cyclodextrin is formed, proving that a single -SH moiety located in the cysteinyl group is sufficient to anchor the entire methylated β-cyclodextrin molecule to the electrode surface. Thus, formed SAM can potentially serve as sensor layer for various organic molecules such as pesticides, antibiotics, and optically active compounds. © 2015 Springer-Verlag Wien.}, keywords = {}, pubstate = {published}, tppubtype = {article} } 6 -Cysteinyl amino methylated β-cyclodextrin was adsorbed on Au(111) as well as on mercury electrode. Scanning probe microscopy and electrochemical techniques confirmed that a chemisorbed self-assembled monolayer (SAM) of the β-cyclodextrin is formed, proving that a single -SH moiety located in the cysteinyl group is sufficient to anchor the entire methylated β-cyclodextrin molecule to the electrode surface. Thus, formed SAM can potentially serve as sensor layer for various organic molecules such as pesticides, antibiotics, and optically active compounds. © 2015 Springer-Verlag Wien. |
Evaluation of monovalent and multivalent iminosugars to modulate Candida albicans β-1,2-mannosyltransferase activities Article de journal T Hurtaux; G Sfihi-Loualia; Y Brissonnet; J Bouckaert; J -M Mallet; B Sendid; F Delplace; E Fabre; S G Gouin; Y Guérardel Carbohydrate Research, 429 , p. 123–127, 2016. @article{Hurtaux:2016, title = {Evaluation of monovalent and multivalent iminosugars to modulate Candida albicans β-1,2-mannosyltransferase activities}, author = {T Hurtaux and G Sfihi-Loualia and Y Brissonnet and J Bouckaert and J -M Mallet and B Sendid and F Delplace and E Fabre and S G Gouin and Y Gu\'{e}rardel}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84956666590&doi=10.1016%2fj.carres.2016.01.004&partnerID=40&md5=aab3c88b7a14fba6bffa454a2ccea6d0}, doi = {10.1016/j.carres.2016.01.004}, year = {2016}, date = {2016-01-01}, journal = {Carbohydrate Research}, volume = {429}, pages = {123--127}, abstract = {β-1,2-Linked oligomannosides substitute the cell wall of numerous yeast species. Several of those including Candida albicans may cause severe infections associated with high rates of morbidity and mortality, especially in immunocompromised patients. β-1,2-Mannosides are known to be involved in the pathogenic process and to elicit an immune response from the host. In C. albicans, the synthesis of β-mannosides is under the control of a family of nine genes coding for putative β-mannosyltransferases. Two of them, CaBmt1 and CaBmt3, have been shown to initiate and prime the elongation of the β-mannosides on the cell-wall mannan core. In the present study, we have assessed the modulating activities of monovalent and multivalent iminosugar analogs on these enzymes in order to control the enzymatic bio-synthesis of β-mannosides. We have identified a monovalent deoxynojirimycin (DNJ) derivative that inhibits the CaBmt1-catalyzed initiating activity, and mono-, tetra- and polyvalent deoxymannojirimycin (DMJ) that modulate the CaBmt1 activity toward the formation of a single major product. Analysis of the aggregating properties of the multivalent iminosugars showed their ability to elicit clusterization of both CaBmt1 and CaBmt3, without affecting their activity. These results suggest promising roles for multivalent iminosugars as controlling agents for the biosynthesis of β-1,2 mannosides and for monovalent DNJ derivative as a first target for the design of future β-mannosyltransferase inhibitors. © 2016 Elsevier Ltd. All rights reserved.}, keywords = {}, pubstate = {published}, tppubtype = {article} } β-1,2-Linked oligomannosides substitute the cell wall of numerous yeast species. Several of those including Candida albicans may cause severe infections associated with high rates of morbidity and mortality, especially in immunocompromised patients. β-1,2-Mannosides are known to be involved in the pathogenic process and to elicit an immune response from the host. In C. albicans, the synthesis of β-mannosides is under the control of a family of nine genes coding for putative β-mannosyltransferases. Two of them, CaBmt1 and CaBmt3, have been shown to initiate and prime the elongation of the β-mannosides on the cell-wall mannan core. In the present study, we have assessed the modulating activities of monovalent and multivalent iminosugar analogs on these enzymes in order to control the enzymatic bio-synthesis of β-mannosides. We have identified a monovalent deoxynojirimycin (DNJ) derivative that inhibits the CaBmt1-catalyzed initiating activity, and mono-, tetra- and polyvalent deoxymannojirimycin (DMJ) that modulate the CaBmt1 activity toward the formation of a single major product. Analysis of the aggregating properties of the multivalent iminosugars showed their ability to elicit clusterization of both CaBmt1 and CaBmt3, without affecting their activity. These results suggest promising roles for multivalent iminosugars as controlling agents for the biosynthesis of β-1,2 mannosides and for monovalent DNJ derivative as a first target for the design of future β-mannosyltransferase inhibitors. © 2016 Elsevier Ltd. All rights reserved. |
Antagonistic Effect of Acetates in C–N Bond Formation with In Situ Generated Diazonium Salts: A Combined Theoretical and Experimental Study Article de journal I Fabre; L A Perego; J Bergès; I Ciofini; L Grimaud; M Taillefer European Journal of Organic Chemistry, 2016 (35), p. 5887–5896, 2016. @article{Fabre:2016, title = {Antagonistic Effect of Acetates in C\textendashN Bond Formation with In Situ Generated Diazonium Salts: A Combined Theoretical and Experimental Study}, author = {I Fabre and L A Perego and J Berg\`{e}s and I Ciofini and L Grimaud and M Taillefer}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85002657035&doi=10.1002%2fejoc.201600891&partnerID=40&md5=ee236c20eefb6f1f6ece9494a9cd139c}, doi = {10.1002/ejoc.201600891}, year = {2016}, date = {2016-01-01}, journal = {European Journal of Organic Chemistry}, volume = {2016}, number = {35}, pages = {5887--5896}, abstract = {The mechanism of the copper-catalyzed arylation of nitrogen heterocycles using anilines via diazonium salts has been studied by combining DFT and experimental data. A CuI/CuIII redox mechanism is proposed. Our study has revealed the multiple roles of the acid/base couple AcOH/AcO\textendash. An in situ formed triazene species maintains a low concentration of diazonium salts in the reaction medium, which ensures limited formation of decomposition products. The results of DFT calculations have explained the lower reactivity of imidazole nucleophiles as compared with pyrazole in the arylation reaction. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim}, keywords = {}, pubstate = {published}, tppubtype = {article} } The mechanism of the copper-catalyzed arylation of nitrogen heterocycles using anilines via diazonium salts has been studied by combining DFT and experimental data. A CuI/CuIII redox mechanism is proposed. Our study has revealed the multiple roles of the acid/base couple AcOH/AcO–. An in situ formed triazene species maintains a low concentration of diazonium salts in the reaction medium, which ensures limited formation of decomposition products. The results of DFT calculations have explained the lower reactivity of imidazole nucleophiles as compared with pyrazole in the arylation reaction. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim |
Mechanistic Studies on the Palladium-Catalyzed Direct C-5 Arylation of Imidazoles: The Fundamental Role of the Azole as a Ligand for Palladium Article de journal L A Perego; L Grimaud; F Bellina Advanced Synthesis and Catalysis, 358 (4), p. 597–609, 2016. @article{Perego:2016, title = {Mechanistic Studies on the Palladium-Catalyzed Direct C-5 Arylation of Imidazoles: The Fundamental Role of the Azole as a Ligand for Palladium}, author = {L A Perego and L Grimaud and F Bellina}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84958765009&doi=10.1002%2fadsc.201500888&partnerID=40&md5=347f25ab343ee17c9163ff0face21def}, doi = {10.1002/adsc.201500888}, year = {2016}, date = {2016-01-01}, journal = {Advanced Synthesis and Catalysis}, volume = {358}, number = {4}, pages = {597--609}, abstract = {An in-depth mechanistic study on the palladium-catalyzed direct arylation of imidazoles at the C-5 position is presented. The interactions of triphenylphosphine (PPh3)-ligated aryl-Pd species with 1,2-dimethyl-1H-imidazole (dmim) have been studied in detail. In contrast with previous suggestions, phosphine-ligated organo-Pd species are not active and the reaction proceeds through imidazole-ligated organo-Pd intermediates. The kinetics of the oxidative addition of aryl halides with dmim-ligated Pd(0) species have been characterized in a Pd(dba)2/dmim model system. A thorough study of the equilibria involving novel [ArPd(dmim)2X] complexes (X=I, OAc) and the unexpected cationic [ArPd(dmim)3]+ is also reported. The ability of these species to effect the C-H arylation of dmim at room temperature in the presence of acetate is also demonstrated. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.}, keywords = {}, pubstate = {published}, tppubtype = {article} } An in-depth mechanistic study on the palladium-catalyzed direct arylation of imidazoles at the C-5 position is presented. The interactions of triphenylphosphine (PPh3)-ligated aryl-Pd species with 1,2-dimethyl-1H-imidazole (dmim) have been studied in detail. In contrast with previous suggestions, phosphine-ligated organo-Pd species are not active and the reaction proceeds through imidazole-ligated organo-Pd intermediates. The kinetics of the oxidative addition of aryl halides with dmim-ligated Pd(0) species have been characterized in a Pd(dba)2/dmim model system. A thorough study of the equilibria involving novel [ArPd(dmim)2X] complexes (X=I, OAc) and the unexpected cationic [ArPd(dmim)3]+ is also reported. The ability of these species to effect the C-H arylation of dmim at room temperature in the presence of acetate is also demonstrated. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
Multiple Roles of Isocyanides in Palladium-Catalyzed Imidoylative Couplings: A Mechanistic Study Article de journal L A Perego; P Fleurat-Lessard; L El Kaïm; I Ciofini; L Grimaud Chemistry - A European Journal, 22 (43), p. 15491–15500, 2016. @article{Perego:2016a, title = {Multiple Roles of Isocyanides in Palladium-Catalyzed Imidoylative Couplings: A Mechanistic Study}, author = {L A Perego and P Fleurat-Lessard and L El Ka\"{i}m and I Ciofini and L Grimaud}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84987936672&doi=10.1002%2fchem.201602913&partnerID=40&md5=9a9ece2d660e15f9e495bcca8fbe847e}, doi = {10.1002/chem.201602913}, year = {2016}, date = {2016-01-01}, journal = {Chemistry - A European Journal}, volume = {22}, number = {43}, pages = {15491--15500}, abstract = {Kinetic, spectroscopic and computational studies examining a palladium-catalyzed imidoylative coupling highlight the dual role of isocyanides as both substrates and ligands for this class of transformations. The synthesis of secondary amides from aryl halides and water is presented as a case study. The kinetics of the oxidative addition of ArI with RNC-ligated Pd0species have been studied and the resulting imidoyl complex [(ArC=NR)Pd(CNR)2I] (Ar=4-F-C6H4}, keywords = {}, pubstate = {published}, tppubtype = {article} } Kinetic, spectroscopic and computational studies examining a palladium-catalyzed imidoylative coupling highlight the dual role of isocyanides as both substrates and ligands for this class of transformations. The synthesis of secondary amides from aryl halides and water is presented as a case study. The kinetics of the oxidative addition of ArI with RNC-ligated Pd0species have been studied and the resulting imidoyl complex [(ArC=NR)Pd(CNR)2I] (Ar=4-F-C6H4 |
Optimized conditions for Passerini-Smiles reactions and applications to benzoxazinone syntheses Article de journal E Martinand-Lurin; A Dos Santos; E Robineau; P Retailleau; P Dauban; L Grimaud; L El Kaïm Molecules, 21 (9), 2016. @article{Martinand-Lurin:2016, title = {Optimized conditions for Passerini-Smiles reactions and applications to benzoxazinone syntheses}, author = {E Martinand-Lurin and A Dos Santos and E Robineau and P Retailleau and P Dauban and L Grimaud and L El Ka\"{i}m}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84988973862&doi=10.3390%2fmolecules21091257&partnerID=40&md5=ae9025719d60f467f4126f08addd11ab}, doi = {10.3390/molecules21091257}, year = {2016}, date = {2016-01-01}, journal = {Molecules}, volume = {21}, number = {9}, abstract = {Initial conditions disclosed for the Passerini-Smiles reaction are associated with a lack of efficiency that has prevented chemists from using it since its discovery. We wish to report herein our thorough study in the development of new experimental conditions for this coupling between electron-poor phenols, isocyanides, and carbonyl derivatives. These new conditions have been applied to several synthetic strategies towards benzoxazinones. © 2016 by the authors; licensee MDPI.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Initial conditions disclosed for the Passerini-Smiles reaction are associated with a lack of efficiency that has prevented chemists from using it since its discovery. We wish to report herein our thorough study in the development of new experimental conditions for this coupling between electron-poor phenols, isocyanides, and carbonyl derivatives. These new conditions have been applied to several synthetic strategies towards benzoxazinones. © 2016 by the authors; licensee MDPI. |
TiCl4-Mediated Preparation of Thiophthalide Derivatives via Formal Thio-Passerini Reactions Article de journal S Ponra; A Nyadanu; L E Kaïm; L Grimaud; M R Vitale Organic Letters, 18 (16), p. 4060–4063, 2016. @article{Ponra:2016, title = {TiCl4-Mediated Preparation of Thiophthalide Derivatives via Formal Thio-Passerini Reactions}, author = {S Ponra and A Nyadanu and L E Ka\"{i}m and L Grimaud and M R Vitale}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84983371914&doi=10.1021%2facs.orglett.6b01937&partnerID=40&md5=83eb6dc235b19ab27683ad9a40a59d52}, doi = {10.1021/acs.orglett.6b01937}, year = {2016}, date = {2016-01-01}, journal = {Organic Letters}, volume = {18}, number = {16}, pages = {4060--4063}, abstract = {By the formal extension of the Passerini reaction to thiocarbonyl derivatives, the straightforward preparation of thiophthalides is disclosed. This method involves the intermediate formation of a sulfanyl-phthalide and a titanium tetrachloride mediated isocyanide insertion reaction. When tert-butyl thiol is used, thanks to the deprotection of the tert-butyl group, a thiophthalide resulting from a 1,5-Mumm rearrangement is isolated. Owing to the multifaceted activity of TiCl4, all steps may conveniently be performed in one pot, starting directly from 2-formylbenzoic acids, tert-butyl thiol, and various isocyanides. © 2016 American Chemical Society.}, keywords = {}, pubstate = {published}, tppubtype = {article} } By the formal extension of the Passerini reaction to thiocarbonyl derivatives, the straightforward preparation of thiophthalides is disclosed. This method involves the intermediate formation of a sulfanyl-phthalide and a titanium tetrachloride mediated isocyanide insertion reaction. When tert-butyl thiol is used, thanks to the deprotection of the tert-butyl group, a thiophthalide resulting from a 1,5-Mumm rearrangement is isolated. Owing to the multifaceted activity of TiCl4, all steps may conveniently be performed in one pot, starting directly from 2-formylbenzoic acids, tert-butyl thiol, and various isocyanides. © 2016 American Chemical Society. |
Influence of the Oxazole Ring Connection on the Fluorescence of Oxazoyl-Triphenylamine Biphotonic DNA Probes Article de journal Blaise Dumat; Elodie Faurel-Paul; Pauline Fornarelli; Nicolas Saettel; Germain Metgé; Céline Fiorini-Debuisschert; Fabrice Charra; Florence Mahuteau-Betzer; Marie-Paule Teulade-Fichou Organic & Biomolecular Chemistry, 14 (1), p. 358-370, 2016. @article{Dumat:2016a, title = {Influence of the Oxazole Ring Connection on the Fluorescence of Oxazoyl-Triphenylamine Biphotonic DNA Probes}, author = {Blaise Dumat and Elodie {Faurel-Paul} and Pauline Fornarelli and Nicolas Saettel and Germain Metg\'{e} and C\'{e}line {Fiorini-Debuisschert} and Fabrice Charra and Florence {Mahuteau-Betzer} and Marie-Paule {Teulade-Fichou}}, doi = {10.1039/C5OB02225H}, year = {2016}, date = {2016-01-01}, journal = {Organic & Biomolecular Chemistry}, volume = {14}, number = {1}, pages = {358-370}, abstract = {The oxazole ring connection of these DNA minor-groove binders strongly impacts their on\textendashoff behavior.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The oxazole ring connection of these DNA minor-groove binders strongly impacts their on–off behavior. |
Mitochondria-Targeted Triphenylamine Derivatives Activatable by Two-Photon Excitation for Triggering and Imaging Cell Apoptosis Article de journal Rahima Chennoufi; Houcine Bougherara; Nathalie Gagey-Eilstein; Blaise Dumat; Etienne Henry; Frédéric Subra; Stéphanie Bury-Moné; Florence Mahuteau-Betzer; Patrick Tauc; Marie-Paule Teulade-Fichou; Eric Deprez Scientific Reports, 6 (January), p. 21458-21458, 2016. @article{Chennoufi:2016, title = {Mitochondria-Targeted Triphenylamine Derivatives Activatable by Two-Photon Excitation for Triggering and Imaging Cell Apoptosis}, author = {Rahima Chennoufi and Houcine Bougherara and Nathalie {Gagey-Eilstein} and Blaise Dumat and Etienne Henry and Fr\'{e}d\'{e}ric Subra and St\'{e}phanie {Bury-Mon\'{e}} and Florence {Mahuteau-Betzer} and Patrick Tauc and Marie-Paule {Teulade-Fichou} and Eric Deprez}, doi = {10.1038/srep21458}, year = {2016}, date = {2016-01-01}, journal = {Scientific Reports}, volume = {6}, number = {January}, pages = {21458-21458}, keywords = {}, pubstate = {published}, tppubtype = {article} } |
Thrombospondin-1 Mimetic Agonist Peptides Induce Selective Death in Tumor Cells: Design, Synthesis, and Structure-Activity Relationship Studies Article de journal T Denèfle; H Boullet; L Herbi; C Newton; A -C Martinez-Torres; A Guez; E Pramil; C Quiney; M Pourcelot; M D Levasseur; E Lardé; R Moumné; F -X Ogi; P Grondin; H Merle-Beral; O Lequin; S A Susin; P Karoyan Journal of Medicinal Chemistry, 59 (18), p. 8412–8421, 2016. @article{Denefle:2016, title = {Thrombospondin-1 Mimetic Agonist Peptides Induce Selective Death in Tumor Cells: Design, Synthesis, and Structure-Activity Relationship Studies}, author = {T Den\`{e}fle and H Boullet and L Herbi and C Newton and A -C Martinez-Torres and A Guez and E Pramil and C Quiney and M Pourcelot and M D Levasseur and E Lard\'{e} and R Moumn\'{e} and F -X Ogi and P Grondin and H Merle-Beral and O Lequin and S A Susin and P Karoyan}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84988735397&doi=10.1021%2facs.jmedchem.6b00781&partnerID=40&md5=56822fdf1d99463527e7e00830952716}, doi = {10.1021/acs.jmedchem.6b00781}, year = {2016}, date = {2016-01-01}, journal = {Journal of Medicinal Chemistry}, volume = {59}, number = {18}, pages = {8412--8421}, abstract = {Thrombospondin-1 (TSP-1) is a glycoprotein considered as a key actor within the tumor microenvironment. Its binding to CD47, a cell surface receptor, triggers programmed cell death. Previous studies allowed the identification of 4N1K decapeptide derived from the TSP-1/CD47 binding epitope. Here, we demonstrate that this peptide is able to induce selective apoptosis of various cancer cell lines while sparing normal cells. A structure-activity relationship study led to the design of the first serum stable TSP-1 mimetic agonist peptide able to trigger selective programmed cell death (PCD) of at least lung, breast, and colorectal cancer cells. Altogether, these results will be of valuable interest for further investigation in the design of potent CD47 agonist peptides, opening new perspectives for the development of original anticancer therapies. © 2016 American Chemical Society.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Thrombospondin-1 (TSP-1) is a glycoprotein considered as a key actor within the tumor microenvironment. Its binding to CD47, a cell surface receptor, triggers programmed cell death. Previous studies allowed the identification of 4N1K decapeptide derived from the TSP-1/CD47 binding epitope. Here, we demonstrate that this peptide is able to induce selective apoptosis of various cancer cell lines while sparing normal cells. A structure-activity relationship study led to the design of the first serum stable TSP-1 mimetic agonist peptide able to trigger selective programmed cell death (PCD) of at least lung, breast, and colorectal cancer cells. Altogether, these results will be of valuable interest for further investigation in the design of potent CD47 agonist peptides, opening new perspectives for the development of original anticancer therapies. © 2016 American Chemical Society. |
Multi-Stage Mass Spectrometry Analysis of Sugar-Conjugated β-Turn Structures to be Used as Probes in Autoimmune Diseases Article de journal C Giangrande; N Auberger; C Rentier; A M Papini; J -M Mallet; S Lavielle; J Vinh Journal of the American Society for Mass Spectrometry, 27 (4), p. 735–747, 2016. @article{Giangrande:2016, title = {Multi-Stage Mass Spectrometry Analysis of Sugar-Conjugated β-Turn Structures to be Used as Probes in Autoimmune Diseases}, author = {C Giangrande and N Auberger and C Rentier and A M Papini and J -M Mallet and S Lavielle and J Vinh}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84962245067&doi=10.1007%2fs13361-015-1321-9&partnerID=40&md5=404714782b302b757b996434cc44a993}, doi = {10.1007/s13361-015-1321-9}, year = {2016}, date = {2016-01-01}, journal = {Journal of the American Society for Mass Spectrometry}, volume = {27}, number = {4}, pages = {735--747}, abstract = {Synthetic sugar-modified peptides were identified as antigenic probes in the context of autoimmune diseases. The aim of this work is to provide a mechanistic study on the fragmentation of different glycosylated analogs of a synthetic antigenic probe able to detect antibodies in a subpopulation of multiple sclerosis patients. In particular the N-glucosylated type I′ β-turn peptide structure called CSF114(Glc) was used as a model to find signature fragmentations exploring the potential of multi-stage mass spectrometry by MALDI-LTQ Orbitrap. Here we compare the fragmentation of the glucosylated form of the synthetic peptide CSF114(Glc), bearing a glucose moiety on an asparagine residue, with less or non- immunoreactive forms, bearing different sugar-modifications, such as CSF114(GlcNAc), modified with a residue of N-acetylglucosamine, and CSF114[Lys7(1-deoxyfructopyranosyl)], this last one modified with a 1-deoxyfructopyranosyl moiety on a lysine at position 7. The analysis was set up using a synthetic compound specifically deuterated on the C-1 to compare its fragmentation with the fragmentation of the undeuterated form, and thus ascertain with confidence the presence on an Asn(Glc) within a peptide sequence. At the end of the study, our analysis led to the identification of signature neutral losses inside the sugar moieties to characterize the different types of glycosylation/glycation. The interest of this study lies in the possibility of applyimg this approach to the discovery of biomarkers and in the diagnosis of autoimmune diseases. © American Society for Mass Spectrometry 2016.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Synthetic sugar-modified peptides were identified as antigenic probes in the context of autoimmune diseases. The aim of this work is to provide a mechanistic study on the fragmentation of different glycosylated analogs of a synthetic antigenic probe able to detect antibodies in a subpopulation of multiple sclerosis patients. In particular the N-glucosylated type I′ β-turn peptide structure called CSF114(Glc) was used as a model to find signature fragmentations exploring the potential of multi-stage mass spectrometry by MALDI-LTQ Orbitrap. Here we compare the fragmentation of the glucosylated form of the synthetic peptide CSF114(Glc), bearing a glucose moiety on an asparagine residue, with less or non- immunoreactive forms, bearing different sugar-modifications, such as CSF114(GlcNAc), modified with a residue of N-acetylglucosamine, and CSF114[Lys7(1-deoxyfructopyranosyl)], this last one modified with a 1-deoxyfructopyranosyl moiety on a lysine at position 7. The analysis was set up using a synthetic compound specifically deuterated on the C-1 to compare its fragmentation with the fragmentation of the undeuterated form, and thus ascertain with confidence the presence on an Asn(Glc) within a peptide sequence. At the end of the study, our analysis led to the identification of signature neutral losses inside the sugar moieties to characterize the different types of glycosylation/glycation. The interest of this study lies in the possibility of applyimg this approach to the discovery of biomarkers and in the diagnosis of autoimmune diseases. © American Society for Mass Spectrometry 2016. |
Identification of an anti-inflammatory protein from Faecalibacterium prausnitzii, a commensal bacterium deficient in Crohn's disease Article de journal E Quévrain; M A Maubert; C Michon; F Chain; R Marquant; J Tailhades; S Miquel; L Carlier; L G Bermúdez-Humarán; B Pigneur; O Lequin; P Kharrat; G Thomas; D Rainteau; C Aubry; N Breyner; C Afonso; S Lavielle; J -P Grill; G Chassaing; J M Chatel; G Trugnan; R Xavier; P Langella; H Sokol; P Seksik Gut, 65 (3), p. 415–425, 2016. @article{Quevrain:2016, title = {Identification of an anti-inflammatory protein from Faecalibacterium prausnitzii, a commensal bacterium deficient in Crohn's disease}, author = {E Qu\'{e}vrain and M A Maubert and C Michon and F Chain and R Marquant and J Tailhades and S Miquel and L Carlier and L G Berm\'{u}dez-Humar\'{a}n and B Pigneur and O Lequin and P Kharrat and G Thomas and D Rainteau and C Aubry and N Breyner and C Afonso and S Lavielle and J -P Grill and G Chassaing and J M Chatel and G Trugnan and R Xavier and P Langella and H Sokol and P Seksik}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84960373289&doi=10.1136%2fgutjnl-2014-307649&partnerID=40&md5=74f8eb656f288a29a96faffebf9c2ee5}, doi = {10.1136/gutjnl-2014-307649}, year = {2016}, date = {2016-01-01}, journal = {Gut}, volume = {65}, number = {3}, pages = {415--425}, abstract = {Background: Crohn's disease (CD)-associated dysbiosis is characterised by a loss of Faecalibacterium prausnitzii, whose culture supernatant exerts an anti-inflammatory effect both in vitro and in vivo. However, the chemical nature of the anti-inflammatory compounds has not yet been determined. Methods: Peptidomic analysis using mass spectrometry was applied to F. prausnitzii supernatant. Antiinflammatory effects of identified peptides were tested in vitro directly on intestinal epithelial cell lines and on cell lines transfected with a plasmid construction coding for the candidate protein encompassing these peptides. In vivo, the cDNA of the candidate protein was delivered to the gut by recombinant lactic acid bacteria to prevent dinitrobenzene sulfonic acid (DNBS)-colitis in mice. Results: The seven peptides, identified in the F. prausnitzii culture supernatants, derived from a single microbial anti-inflammatory molecule (MAM), a protein of 15 kDa, and comprising 53% of non-polar residues. This last feature prevented the direct characterisation of the putative anti-inflammatory activity of MAM-derived peptides. Transfection of MAM cDNA in epithelial cells led to a significant decrease in the activation of the nuclear factor (NF)-?B pathway with a dose-dependent effect. Finally, the use of a food-grade bacterium, Lactococcus lactis, delivering a plasmid encoding MAM was able to alleviate DNBS-induced colitis in mice. Conclusions: A 15 kDa protein with anti-inflammatory properties is produced by F. prausnitzii, a commensal bacterium involved in CD pathogenesis. This protein is able to inhibit the NF-κB pathway in intestinal epithelial cells and to prevent colitis in an animal model.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background: Crohn's disease (CD)-associated dysbiosis is characterised by a loss of Faecalibacterium prausnitzii, whose culture supernatant exerts an anti-inflammatory effect both in vitro and in vivo. However, the chemical nature of the anti-inflammatory compounds has not yet been determined. Methods: Peptidomic analysis using mass spectrometry was applied to F. prausnitzii supernatant. Antiinflammatory effects of identified peptides were tested in vitro directly on intestinal epithelial cell lines and on cell lines transfected with a plasmid construction coding for the candidate protein encompassing these peptides. In vivo, the cDNA of the candidate protein was delivered to the gut by recombinant lactic acid bacteria to prevent dinitrobenzene sulfonic acid (DNBS)-colitis in mice. Results: The seven peptides, identified in the F. prausnitzii culture supernatants, derived from a single microbial anti-inflammatory molecule (MAM), a protein of 15 kDa, and comprising 53% of non-polar residues. This last feature prevented the direct characterisation of the putative anti-inflammatory activity of MAM-derived peptides. Transfection of MAM cDNA in epithelial cells led to a significant decrease in the activation of the nuclear factor (NF)-?B pathway with a dose-dependent effect. Finally, the use of a food-grade bacterium, Lactococcus lactis, delivering a plasmid encoding MAM was able to alleviate DNBS-induced colitis in mice. Conclusions: A 15 kDa protein with anti-inflammatory properties is produced by F. prausnitzii, a commensal bacterium involved in CD pathogenesis. This protein is able to inhibit the NF-κB pathway in intestinal epithelial cells and to prevent colitis in an animal model. |
How to unveil self-quenched fluorophores and subsequently map the subcellular distribution of exogenous peptides Article de journal J -M Swiecicki; F Thiebaut; M Di Pisa; S Gourdin -Bertin; J Tailhades; C Mansuy; F Burlina; S Chwetzoff; G Trugnan; G Chassaing; S Lavielle Scientific Reports, 6 , 2016. @article{Swiecicki:2016, title = {How to unveil self-quenched fluorophores and subsequently map the subcellular distribution of exogenous peptides}, author = {J -M Swiecicki and F Thiebaut and M Di Pisa and S Gourdin -Bertin and J Tailhades and C Mansuy and F Burlina and S Chwetzoff and G Trugnan and G Chassaing and S Lavielle}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84957837107&doi=10.1038%2fsrep20237&partnerID=40&md5=3b6ebb5cc1852323b58fc293948a9914}, doi = {10.1038/srep20237}, year = {2016}, date = {2016-01-01}, journal = {Scientific Reports}, volume = {6}, abstract = {Confocal laser scanning microscopy (CLSM) is the most popular technique for mapping the subcellular distribution of a fluorescent molecule and is widely used to investigate the penetration properties of exogenous macromolecules, such as cell-penetrating peptides (CPPs), within cells. Despite the membrane-association propensity of all these CPPs, the signal of the fluorescently labeled CPPs did not colocalize with the plasma membrane. We studied the origin of this fluorescence extinction and the overall consequence on the interpretation of intracellular localizations from CLSM pictures. We demonstrated that this discrepancy originated from fluorescence self-quenching. The fluorescence was unveiled by a "dilution" protocol, i.e. by varying the ratio fluorescent/non-fluorescent CPP. This strategy allowed us to rank with confidence the subcellular distribution of several CPPs, contributing to the elucidation of the penetration mechanism. More generally, this study proposes a broadly applicable and reliable method to study the subcellular distribution of any fluorescently labeled molecules.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Confocal laser scanning microscopy (CLSM) is the most popular technique for mapping the subcellular distribution of a fluorescent molecule and is widely used to investigate the penetration properties of exogenous macromolecules, such as cell-penetrating peptides (CPPs), within cells. Despite the membrane-association propensity of all these CPPs, the signal of the fluorescently labeled CPPs did not colocalize with the plasma membrane. We studied the origin of this fluorescence extinction and the overall consequence on the interpretation of intracellular localizations from CLSM pictures. We demonstrated that this discrepancy originated from fluorescence self-quenching. The fluorescence was unveiled by a "dilution" protocol, i.e. by varying the ratio fluorescent/non-fluorescent CPP. This strategy allowed us to rank with confidence the subcellular distribution of several CPPs, contributing to the elucidation of the penetration mechanism. More generally, this study proposes a broadly applicable and reliable method to study the subcellular distribution of any fluorescently labeled molecules. |
Isomerization and Oligomerization of Truncated and Mutated Tau Forms by FKBP52 are Independent Processes Article de journal A Kamah; F X Cantrelle; I Huvent; J Giustiniani; K Guillemeau; C Byrne; Y Jacquot; I Landrieu; E E Baulieu; C Smet; B Chambraud; G Lippens Journal of Molecular Biology, 428 (6), p. 1080–1090, 2016. @article{Kamah:2016, title = {Isomerization and Oligomerization of Truncated and Mutated Tau Forms by FKBP52 are Independent Processes}, author = {A Kamah and F X Cantrelle and I Huvent and J Giustiniani and K Guillemeau and C Byrne and Y Jacquot and I Landrieu and E E Baulieu and C Smet and B Chambraud and G Lippens}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84959261786&doi=10.1016%2fj.jmb.2016.02.015&partnerID=40&md5=fa8b175818d6093a38424aca150b0eb2}, doi = {10.1016/j.jmb.2016.02.015}, year = {2016}, date = {2016-01-01}, journal = {Journal of Molecular Biology}, volume = {428}, number = {6}, pages = {1080--1090}, abstract = {The aggregation of the neuronal Tau protein is one molecular hallmark of Alzheimer's disease and other related tauopathies, but the precise molecular mechanisms of the aggregation process remain unclear. The FK506 binding protein FKBP52 is able to induce oligomers in the pathogenic Tau P301L mutant and in a truncated form of the wild-type human Tau protein. Here, we investigate whether FKBP52's capacity to induce Tau oligomers depends on its prolyl cis/trans isomerase activity. We find that FKBP52 indeed can isomerize selected prolyl bonds in the different Tau proteins, and that this activity is carried solely by its first FK506 binding domain. Its capacity to oligomerize Tau is, however, not linked to this peptidyl-prolyl isomerase activity. In addition, we identified a novel molecular interaction implying the PHF6 peptide of Tau and the FK1/FK2 domains of FKBP52 independent of FK506 binding; these data point toward a non-catalytic molecular interaction that might govern the effect of FKBP52 on Tau. © 2016 Elsevier Ltd. All rights reserved.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The aggregation of the neuronal Tau protein is one molecular hallmark of Alzheimer's disease and other related tauopathies, but the precise molecular mechanisms of the aggregation process remain unclear. The FK506 binding protein FKBP52 is able to induce oligomers in the pathogenic Tau P301L mutant and in a truncated form of the wild-type human Tau protein. Here, we investigate whether FKBP52's capacity to induce Tau oligomers depends on its prolyl cis/trans isomerase activity. We find that FKBP52 indeed can isomerize selected prolyl bonds in the different Tau proteins, and that this activity is carried solely by its first FK506 binding domain. Its capacity to oligomerize Tau is, however, not linked to this peptidyl-prolyl isomerase activity. In addition, we identified a novel molecular interaction implying the PHF6 peptide of Tau and the FK1/FK2 domains of FKBP52 independent of FK506 binding; these data point toward a non-catalytic molecular interaction that might govern the effect of FKBP52 on Tau. © 2016 Elsevier Ltd. All rights reserved. |
A β-turn motif in the steroid hormone receptor's ligand-binding domains interacts with the peptidyl-prolyl isomerase (PPIase) catalytic site of the immunophilin FKBP52 Article de journal C Byrne; M A Henen; M Belnou; F -X Cantrelle; A Kamah; H Qi; J Giustiniani; B Chambraud; E -E Baulieu; G Lippens; I Landrieu; Y Jacquot Biochemistry, 55 (38), p. 5366–5376, 2016. @article{Byrne:2016, title = {A β-turn motif in the steroid hormone receptor's ligand-binding domains interacts with the peptidyl-prolyl isomerase (PPIase) catalytic site of the immunophilin FKBP52}, author = {C Byrne and M A Henen and M Belnou and F -X Cantrelle and A Kamah and H Qi and J Giustiniani and B Chambraud and E -E Baulieu and G Lippens and I Landrieu and Y Jacquot}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84989260723&doi=10.1021%2facs.biochem.6b00506&partnerID=40&md5=d6d3646263e00c9bd3049c235c894a13}, doi = {10.1021/acs.biochem.6b00506}, year = {2016}, date = {2016-01-01}, journal = {Biochemistry}, volume = {55}, number = {38}, pages = {5366--5376}, abstract = {The immunophilin FKBP52 interacts with nuclear steroid hormone receptors. Studying the crystal structure of human estrogen receptor α (hERα) and using nuclear magnetic resonance, we show here that the short V364PGF367 sequence, which is located within its ligand-binding domain and adopts a type II β-turn conformation in the protein, binds the peptidyl-prolyl isomerase (PPIase or rotamase) FK1 domain of FKBP52. Interestingly, this turn motif displays strong similarities with the FKBP52 FK1 domain-binding moiety of macrolide immunomodulators such as rapamycin and GPI-1046, an immunophilin ligand with neuroprotective characteristics. An increase in the hydrophobicity of the residue preceding the proline and cyclization of the VPGF peptide strengthen its recognition by the FK1 domain of FKBP52. Replacement of the Pro residue with a dimethylproline also enhances this interaction. Our study not only contributes to a better understanding of how the interaction between the FK1 domain of FKBP52 and steroid hormone receptors most likely works but also opens new avenues for the synthesis of FKBP52 FK1 peptide ligands appropriate for the control of hormone-dependent physiological mechanisms or of the functioning of the Tau protein. Indeed, it has been shown that FKBP52 is involved in the intraneuronal dynamics of the Tau protein. © 2016 American Chemical Society.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The immunophilin FKBP52 interacts with nuclear steroid hormone receptors. Studying the crystal structure of human estrogen receptor α (hERα) and using nuclear magnetic resonance, we show here that the short V364PGF367 sequence, which is located within its ligand-binding domain and adopts a type II β-turn conformation in the protein, binds the peptidyl-prolyl isomerase (PPIase or rotamase) FK1 domain of FKBP52. Interestingly, this turn motif displays strong similarities with the FKBP52 FK1 domain-binding moiety of macrolide immunomodulators such as rapamycin and GPI-1046, an immunophilin ligand with neuroprotective characteristics. An increase in the hydrophobicity of the residue preceding the proline and cyclization of the VPGF peptide strengthen its recognition by the FK1 domain of FKBP52. Replacement of the Pro residue with a dimethylproline also enhances this interaction. Our study not only contributes to a better understanding of how the interaction between the FK1 domain of FKBP52 and steroid hormone receptors most likely works but also opens new avenues for the synthesis of FKBP52 FK1 peptide ligands appropriate for the control of hormone-dependent physiological mechanisms or of the functioning of the Tau protein. Indeed, it has been shown that FKBP52 is involved in the intraneuronal dynamics of the Tau protein. © 2016 American Chemical Society. |