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.
2012 |
Glycosiderophores: Synthesis of tris-hydroxamate siderophores based on a galactose or glycero central scaffold, Fe(III) complexation studies Article de journal C Neff; F Bellot; J -B Waern; F Lambert; J Brandel; G Serratrice; F Gaboriau; C Policar Journal of Inorganic Biochemistry, 112 , p. 59–67, 2012. @article{Neff:2012, title = {Glycosiderophores: Synthesis of tris-hydroxamate siderophores based on a galactose or glycero central scaffold, Fe(III) complexation studies}, author = {C Neff and F Bellot and J -B Waern and F Lambert and J Brandel and G Serratrice and F Gaboriau and C Policar}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84860271202&doi=10.1016%2fj.jinorgbio.2012.02.030&partnerID=40&md5=67094ead67163b2ab05f9eed02b54bbd}, doi = {10.1016/j.jinorgbio.2012.02.030}, year = {2012}, date = {2012-01-01}, journal = {Journal of Inorganic Biochemistry}, volume = {112}, pages = {59--67}, abstract = {A series of five new hexadentate tris-hydroxamate ligands based on a d-galactose or a glycerol scaffold have been synthesized. Protonation and ferric complex formation constants have been determined from solution studies by potentiometric and spectrophotometric titrations. All ligands form 1:1 Fe:L complexes. The calculated pFe values at pH 7.4 span over the range 19.2-23.0 depending on the scaffold and on the length of the spacers between hydroxamate and central scaffold and on the N-methyl substitution. This new kind of artificial siderophores based on a glycoscaffold is of interest as it opens up an easy way to modulate the pFe. © 2012 Elsevier Inc.}, keywords = {}, pubstate = {published}, tppubtype = {article} } A series of five new hexadentate tris-hydroxamate ligands based on a d-galactose or a glycerol scaffold have been synthesized. Protonation and ferric complex formation constants have been determined from solution studies by potentiometric and spectrophotometric titrations. All ligands form 1:1 Fe:L complexes. The calculated pFe values at pH 7.4 span over the range 19.2-23.0 depending on the scaffold and on the length of the spacers between hydroxamate and central scaffold and on the N-methyl substitution. This new kind of artificial siderophores based on a glycoscaffold is of interest as it opens up an easy way to modulate the pFe. © 2012 Elsevier Inc. |
Recent analytical applications of molecular spectroscopy in bioorganometallic chemistrypart I: Metal carbonyls Article de journal I S Butler; R P Kengne-Momo; G Jaouen; C Policar; A Vessières Applied Spectroscopy Reviews, 47 (7), p. 531–549, 2012. @article{Butler:2012, title = {Recent analytical applications of molecular spectroscopy in bioorganometallic chemistrypart I: Metal carbonyls}, author = {I S Butler and R P Kengne-Momo and G Jaouen and C Policar and A Vessi\`{e}res}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84865204418&doi=10.1080%2f05704928.2012.673189&partnerID=40&md5=520598e533375e3ff67b73f9e50d4386}, doi = {10.1080/05704928.2012.673189}, year = {2012}, date = {2012-01-01}, journal = {Applied Spectroscopy Reviews}, volume = {47}, number = {7}, pages = {531--549}, abstract = {This is the first part of a two-part review on the analytical applications of molecular spectroscopy in bioorganometallic chemistry since 2005. In this case, radiopharmaceutical studies are included and the review is focused particularly on biological molecules labeled with metal carbonyl fragments. Copyright © Taylor & Francis Group, LLC.}, keywords = {}, pubstate = {published}, tppubtype = {article} } This is the first part of a two-part review on the analytical applications of molecular spectroscopy in bioorganometallic chemistry since 2005. In this case, radiopharmaceutical studies are included and the review is focused particularly on biological molecules labeled with metal carbonyl fragments. Copyright © Taylor & Francis Group, LLC. |
Recent applications of molecular spectroscopy in bioorganometallic chemistry-Part 2: Ferrocenes and other organometallic complexes Article de journal I S Butler; R P Kengne-Momo; A Vessières; G Jaouen; C Policar Applied Spectroscopy Reviews, 47 (8), p. 620–632, 2012. @article{Butler:2012a, title = {Recent applications of molecular spectroscopy in bioorganometallic chemistry-Part 2: Ferrocenes and other organometallic complexes}, author = {I S Butler and R P Kengne-Momo and A Vessi\`{e}res and G Jaouen and C Policar}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84867002904&doi=10.1080%2f05704928.2012.697088&partnerID=40&md5=9a894613d259bfe47cd1f47469a86497}, doi = {10.1080/05704928.2012.697088}, year = {2012}, date = {2012-01-01}, journal = {Applied Spectroscopy Reviews}, volume = {47}, number = {8}, pages = {620--632}, abstract = {This is the second part of an overview of the applications of the various molecular spectroscopic methods that have been employed in bioorganometallic chemistry research since 2005 focusing on ferrocenes and other non-metal carbonyl organometallic complexes. These spectroscopic methods encompass infrared (IR), nuclear magnetic resonance (NMR), mass, Raman, ultraviolet-visible (UV-Vis), and several other less common spectroscopic techniques. © 2012 Taylor & Francis Group, LLC.}, keywords = {}, pubstate = {published}, tppubtype = {article} } This is the second part of an overview of the applications of the various molecular spectroscopic methods that have been employed in bioorganometallic chemistry research since 2005 focusing on ferrocenes and other non-metal carbonyl organometallic complexes. These spectroscopic methods encompass infrared (IR), nuclear magnetic resonance (NMR), mass, Raman, ultraviolet-visible (UV-Vis), and several other less common spectroscopic techniques. © 2012 Taylor & Francis Group, LLC. |
Metal complexation of a Đ -ribose-based ligand decoded by experimental and theoretical studies Article de journal F Cisnetti; J -D Maréchal; M Nicaise; R Guillot; M Desmadril; F Lambert; C Policar European Journal of Inorganic Chemistry, (20), p. 3308–3319, 2012. @article{Cisnetti:2012, title = {Metal complexation of a {D} -ribose-based ligand decoded by experimental and theoretical studies}, author = {F Cisnetti and J -D Mar\'{e}chal and M Nicaise and R Guillot and M Desmadril and F Lambert and C Policar}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84863687434&doi=10.1002%2fejic.201200322&partnerID=40&md5=0682fc752866de140dd4439a4be02cdd}, doi = {10.1002/ejic.201200322}, year = {2012}, date = {2012-01-01}, journal = {European Journal of Inorganic Chemistry}, number = {20}, pages = {3308--3319}, abstract = {A combination of experimental and theoretical methods have been used to elucidate the complexation properties of a new sugar-derived hexadentate ligand, namely methyl 2,3,4-tri-O-(2-picolyl)-β-D-ribopyranoside (L). The coordination bond lengths in the complexes with Mn II, Co II, Ni II, and Zn II show substantial deviations from ideal octahedra with deformation towards trigonal-prismatic geometries, which is indicative of a conformationally constrained ligand. The metal-cation-ligand interactions were studied for L and the acyclic analogue L' [1,2,3-tri-O-(2-picolyl)-1,2,3-propanetriol] by spectroscopic methods and isothermal calorimetric titrations for the series Mn II, Co II, Ni II, Zn II, and Cu II. The results indicate a stabilization of the complexes obtained with L compared with L', depending on the nature of the metal. Molecular modeling studies showed that the presence of the sugar moiety strongly favors conformations compatible with metal binding, which suggests an entropic origin of the stabilization of L complexes with regards to L' complexes. Moreover, the differences in the metal chelation profiles of L and L' are related to the constraints in the sugar group in the metal-bound structures. This study shows that foreseeing the degree of preorganization of flexible ligands may drive the design of a new generation of chelating compounds. A new sugar-derived ligand, with its coordination site embedded in a pyranoside cycle in the chair conformation, has been designed. Its transition-metal complexes were characterized by experimental and complexation methods and revealed a dramatic impact of the preorganization and complementarity of the carbohydrate scaffold on the metal binding. © 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.}, keywords = {}, pubstate = {published}, tppubtype = {article} } A combination of experimental and theoretical methods have been used to elucidate the complexation properties of a new sugar-derived hexadentate ligand, namely methyl 2,3,4-tri-O-(2-picolyl)-β-D-ribopyranoside (L). The coordination bond lengths in the complexes with Mn II, Co II, Ni II, and Zn II show substantial deviations from ideal octahedra with deformation towards trigonal-prismatic geometries, which is indicative of a conformationally constrained ligand. The metal-cation-ligand interactions were studied for L and the acyclic analogue L' [1,2,3-tri-O-(2-picolyl)-1,2,3-propanetriol] by spectroscopic methods and isothermal calorimetric titrations for the series Mn II, Co II, Ni II, Zn II, and Cu II. The results indicate a stabilization of the complexes obtained with L compared with L', depending on the nature of the metal. Molecular modeling studies showed that the presence of the sugar moiety strongly favors conformations compatible with metal binding, which suggests an entropic origin of the stabilization of L complexes with regards to L' complexes. Moreover, the differences in the metal chelation profiles of L and L' are related to the constraints in the sugar group in the metal-bound structures. This study shows that foreseeing the degree of preorganization of flexible ligands may drive the design of a new generation of chelating compounds. A new sugar-derived ligand, with its coordination site embedded in a pyranoside cycle in the chair conformation, has been designed. Its transition-metal complexes were characterized by experimental and complexation methods and revealed a dramatic impact of the preorganization and complementarity of the carbohydrate scaffold on the metal binding. © 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. |
Biotin sulfone tagged oligomannosides as immunogens for eliciting antibodies against specific mannan epitopes Article de journal G Despras; R Robert; B Sendid; E MacHez; D Poulain; J -M Mallet Bioorganic and Medicinal Chemistry, 20 (5), p. 1817–1831, 2012. @article{Despras:2012, title = {Biotin sulfone tagged oligomannosides as immunogens for eliciting antibodies against specific mannan epitopes}, author = {G Despras and R Robert and B Sendid and E MacHez and D Poulain and J -M Mallet}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-84857360125&doi=10.1016%2fj.bmc.2011.12.048&partnerID=40&md5=0b7cb6af1d7c3691372c2dd322a3f07a}, doi = {10.1016/j.bmc.2011.12.048}, year = {2012}, date = {2012-01-01}, journal = {Bioorganic and Medicinal Chemistry}, volume = {20}, number = {5}, pages = {1817--1831}, abstract = {Biotinylated tri and tetrasaccharide: α Man (1→3) α Man (1→2) α Man; α Man (1→3) α Man (1→2) α Man (1→2) α Man were prepared using methyl tertbutyl phenyl thioglycosides glycosyl donors (MBP) and biotin sulfone strategy. Three key mannosyl thioglycosidic donors have been prepared: one for 1→2 linkage and two for the 1→3 linkage (protected with a 4,6-O-benzylidene or a 4,6-di-O-benzyl). The benzyliden protected one was not found reactive enough, and the benzylated donor was preferred. These biotinylated oligomanosides were evaluated as antigen in Crohn disease diagnosis and used coupled to streptavidin as hapten for eliciting polyclonal antibodies in mice. © 2012 Elsevier Ltd. All rights reserved.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Biotinylated tri and tetrasaccharide: α Man (1→3) α Man (1→2) α Man; α Man (1→3) α Man (1→2) α Man (1→2) α Man were prepared using methyl tertbutyl phenyl thioglycosides glycosyl donors (MBP) and biotin sulfone strategy. Three key mannosyl thioglycosidic donors have been prepared: one for 1→2 linkage and two for the 1→3 linkage (protected with a 4,6-O-benzylidene or a 4,6-di-O-benzyl). The benzyliden protected one was not found reactive enough, and the benzylated donor was preferred. These biotinylated oligomanosides were evaluated as antigen in Crohn disease diagnosis and used coupled to streptavidin as hapten for eliciting polyclonal antibodies in mice. © 2012 Elsevier Ltd. All rights reserved. |
2011 |
β-Amino acids containing peptides and click-cyclized peptide as β-turn mimics: A comparative study with 'conventional' lactam- and disulfide-bridged hexapeptides Article de journal M Larregola; O Lequin; P Karoyan; D Guianvarc'h; S Lavielle Journal of Peptide Science, 17 (9), p. 632–643, 2011. @article{Larregola:2011, title = {β-Amino acids containing peptides and click-cyclized peptide as β-turn mimics: A comparative study with 'conventional' lactam- and disulfide-bridged hexapeptides}, author = {M Larregola and O Lequin and P Karoyan and D Guianvarc'h and S Lavielle}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-79961171300&doi=10.1002%2fpsc.1382&partnerID=40&md5=5827ac591a99fb61fadafefafddf197d}, doi = {10.1002/psc.1382}, year = {2011}, date = {2011-01-01}, journal = {Journal of Peptide Science}, volume = {17}, number = {9}, pages = {632--643}, abstract = {The increasing interest in click chemistry and its use to stabilize turn structures led us to compare the propensity for β-turn stabilization of different analogs designed as mimics of the β-turn structure found in tendamistat. The β-turn conformation of linear β-amino acid-containing peptides and triazole-cyclized analogs were compared to 'conventional' lactam- and disulfide-bridged hexapeptide analogs. Their 3D structures and their propensity to fold in β-turns in solution, and for those not structured in solution in the presence of α-amylase, were analyzed by NMR spectroscopy and by restrained molecular dynamics with energy minimization. The linear tetrapeptide Ac-Ser-Trp-Arg-Tyr-NH 2 and both the amide bond-cyclized, c[Pro-Ser-Trp-Arg-Tyr-D-Ala] and the disulfide-bridged, Ac-c[Cys-Ser-Trp-Arg-Tyr-Cys]-NH 2 hexapeptides adopt dominantly in solution a β-turn conformation closely related to the one observed in tendamistat. On the contrary, the β-amino acid-containing peptides such as Ac-(R)-β 3-hSer-(S)-Trp-(S)-β 3-hArg-(S)-β 3-hTyr-NH 2, and the triazole cyclic peptide, c[Lys-Ser-Trp-Arg-Tyr-βtA]-NH 2, both specifically designed to mimic this β-turn, do not adopt stable structures in solution and do not show any characteristics of β-turn conformation. However, these unstructured peptides specifically interact in the active site of α-amylase, as shown by TrNOESY and saturation transfer difference NMR experiments performed in the presence of the enzyme, and are displaced by acarbose, a specific α-amylase inhibitor. Thus, in contrast to amide-cyclized or disulfide-bridged hexapeptides, β-amino acid-containing peptides and click-cyclized peptides may not be regarded as β-turn stabilizers, but can be considered as potential β-turn inducers. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The increasing interest in click chemistry and its use to stabilize turn structures led us to compare the propensity for β-turn stabilization of different analogs designed as mimics of the β-turn structure found in tendamistat. The β-turn conformation of linear β-amino acid-containing peptides and triazole-cyclized analogs were compared to 'conventional' lactam- and disulfide-bridged hexapeptide analogs. Their 3D structures and their propensity to fold in β-turns in solution, and for those not structured in solution in the presence of α-amylase, were analyzed by NMR spectroscopy and by restrained molecular dynamics with energy minimization. The linear tetrapeptide Ac-Ser-Trp-Arg-Tyr-NH 2 and both the amide bond-cyclized, c[Pro-Ser-Trp-Arg-Tyr-D-Ala] and the disulfide-bridged, Ac-c[Cys-Ser-Trp-Arg-Tyr-Cys]-NH 2 hexapeptides adopt dominantly in solution a β-turn conformation closely related to the one observed in tendamistat. On the contrary, the β-amino acid-containing peptides such as Ac-(R)-β 3-hSer-(S)-Trp-(S)-β 3-hArg-(S)-β 3-hTyr-NH 2, and the triazole cyclic peptide, c[Lys-Ser-Trp-Arg-Tyr-βtA]-NH 2, both specifically designed to mimic this β-turn, do not adopt stable structures in solution and do not show any characteristics of β-turn conformation. However, these unstructured peptides specifically interact in the active site of α-amylase, as shown by TrNOESY and saturation transfer difference NMR experiments performed in the presence of the enzyme, and are displaced by acarbose, a specific α-amylase inhibitor. Thus, in contrast to amide-cyclized or disulfide-bridged hexapeptides, β-amino acid-containing peptides and click-cyclized peptides may not be regarded as β-turn stabilizers, but can be considered as potential β-turn inducers. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd. |
The Combination of Prolinoamino Acids and Cyclopropylamino Acids Leads to Fully Functionalized, Stable β-Turns in Water Article de journal K Guitot; M Larregola; T K Pradhan; J -L Vasse; S Lavielle; P Bertus; J Szymoniak; O Lequin; P Karoyan ChemBioChem, 12 (7), p. 1039–1042, 2011. @article{Guitot:2011, title = {The Combination of Prolinoamino Acids and Cyclopropylamino Acids Leads to Fully Functionalized, Stable β-Turns in Water}, author = {K Guitot and M Larregola and T K Pradhan and J -L Vasse and S Lavielle and P Bertus and J Szymoniak and O Lequin and P Karoyan}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-79955057486&doi=10.1002%2fcbic.201000707&partnerID=40&md5=e9ec258bc831d744185ba628bcdfa3e3}, doi = {10.1002/cbic.201000707}, year = {2011}, date = {2011-01-01}, journal = {ChemBioChem}, volume = {12}, number = {7}, pages = {1039--1042}, abstract = {Tight turns: Peptide mimics based on combinations of cis-3-prolinoamino acids (prolinohomotryptophan) and (Z)-2,3-methanoamino acids (c3Arg or c3Lys) form stable β-turns in water. This combination of constraints allows one to mimic turns with side chain conformations not accessible with the previously reported strategy involving combinations of prolinoamino acids and N-methylamino acids. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Tight turns: Peptide mimics based on combinations of cis-3-prolinoamino acids (prolinohomotryptophan) and (Z)-2,3-methanoamino acids (c3Arg or c3Lys) form stable β-turns in water. This combination of constraints allows one to mimic turns with side chain conformations not accessible with the previously reported strategy involving combinations of prolinoamino acids and N-methylamino acids. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
Peptides for intracellular pharmacology Article de journal G Chassaing; S Lavielle Actualite Chimique, (353-354), p. 97–99, 2011. @article{Chassaing:2011, title = {Peptides for intracellular pharmacology}, author = {G Chassaing and S Lavielle}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-80053920411&partnerID=40&md5=6bdf3e8327054d87a0adab467a42d7ea}, year = {2011}, date = {2011-01-01}, journal = {Actualite Chimique}, number = {353-354}, pages = {97--99}, abstract = {It was established some twenty years ago that cationic peptides, bearing several positive charges, could enter a cell meaning that they were capable to cross the lipid bilayer. Moreover, these peptides, called cell penetrating peptides (CPP), are able to convey in a cell another molecule, which by itself will not penetrate into the cell; these molecules are called cargoes. This discovery, which has knocked down the dogma on the impermeability of the plasma membrane to charged species, has opened an avenue to an intracellular pharmacology. While the penetration mechanism(s) is (are) still subject to controversy, the potential of this strategy is now explored in parallel to other vectorization strategies based on nanoparticles (liposomes, polymers or other colloids.).}, keywords = {}, pubstate = {published}, tppubtype = {article} } It was established some twenty years ago that cationic peptides, bearing several positive charges, could enter a cell meaning that they were capable to cross the lipid bilayer. Moreover, these peptides, called cell penetrating peptides (CPP), are able to convey in a cell another molecule, which by itself will not penetrate into the cell; these molecules are called cargoes. This discovery, which has knocked down the dogma on the impermeability of the plasma membrane to charged species, has opened an avenue to an intracellular pharmacology. While the penetration mechanism(s) is (are) still subject to controversy, the potential of this strategy is now explored in parallel to other vectorization strategies based on nanoparticles (liposomes, polymers or other colloids.). |
Nanodiamond as a vector for siRNA delivery to Ewing sarcoma cells Article de journal A Alhaddad; M -P Adam; J Botsoa; G Dantelle; S Perruchas; T Gacoin; C Mansuy; S Lavielle; C Malvy; F Treussart; J -R Bertrand Small, 7 (21), p. 3087–3095, 2011. @article{Alhaddad:2011, title = {Nanodiamond as a vector for siRNA delivery to Ewing sarcoma cells}, author = {A Alhaddad and M -P Adam and J Botsoa and G Dantelle and S Perruchas and T Gacoin and C Mansuy and S Lavielle and C Malvy and F Treussart and J -R Bertrand}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-80155151294&doi=10.1002%2fsmll.201101193&partnerID=40&md5=2cf65b5cb0918112146ff9faf4f6c390}, doi = {10.1002/smll.201101193}, year = {2011}, date = {2011-01-01}, journal = {Small}, volume = {7}, number = {21}, pages = {3087--3095}, abstract = {The ability of diamond nanoparticles (nanodiamonds, NDs) to deliver small interfering RNA (siRNA) into Ewing sarcoma cells is investigated with a view to the possibility of in-vivo anticancer nucleic-acid drug delivery. siRNA is adsorbed onto NDs that are coated with cationic polymer. Cell uptake of NDs is demonstrated by taking advantage of the NDs' intrinsic fluorescence from embedded color-center defects. Cell toxicity of these coated NDs is shown to be low. Consistent with the internalization efficacy, a specific inhibition of EWS/Fli-1 gene expression is shown at the mRNA and protein level by the ND-vectorized siRNA in a serum-containing medium. Embedded color-center defects are used to monitor intrinsic nanodiamond (ND) fluorescence less than 24 h after the release of their FITC-labeled small interfering RNA (siRNA) cargo into Ewing sarcoma cells. The siRNA is delivered after adsorption onto NDs that have been coated with a cationic polymer. The use of NDs as siRNA delivery vehicles points to the possibility of in-vivo anticancer nucleic-acid drug delivery. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The ability of diamond nanoparticles (nanodiamonds, NDs) to deliver small interfering RNA (siRNA) into Ewing sarcoma cells is investigated with a view to the possibility of in-vivo anticancer nucleic-acid drug delivery. siRNA is adsorbed onto NDs that are coated with cationic polymer. Cell uptake of NDs is demonstrated by taking advantage of the NDs' intrinsic fluorescence from embedded color-center defects. Cell toxicity of these coated NDs is shown to be low. Consistent with the internalization efficacy, a specific inhibition of EWS/Fli-1 gene expression is shown at the mRNA and protein level by the ND-vectorized siRNA in a serum-containing medium. Embedded color-center defects are used to monitor intrinsic nanodiamond (ND) fluorescence less than 24 h after the release of their FITC-labeled small interfering RNA (siRNA) cargo into Ewing sarcoma cells. The siRNA is delivered after adsorption onto NDs that have been coated with a cationic polymer. The use of NDs as siRNA delivery vehicles points to the possibility of in-vivo anticancer nucleic-acid drug delivery. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
Peptides targeting estrogen receptor alpha-potential applications for breast cancer treatment Article de journal G Leclercq; D Gallo; J Cossy; I Laïos; D Larsimont; G Laurent; Y Jacquot Current Pharmaceutical Design, 17 (25), p. 2632–2653, 2011. @article{Leclercq:2011, title = {Peptides targeting estrogen receptor alpha-potential applications for breast cancer treatment}, author = {G Leclercq and D Gallo and J Cossy and I La\"{i}os and D Larsimont and G Laurent and Y Jacquot}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-80053521414&doi=10.2174%2f138161211797416048&partnerID=40&md5=34f5b25e786c991b8e582082e7d81f0f}, doi = {10.2174/138161211797416048}, year = {2011}, date = {2011-01-01}, journal = {Current Pharmaceutical Design}, volume = {17}, number = {25}, pages = {2632--2653}, abstract = {Activation of the estrogen receptor alpha (ERα) is of prime importance for the development of hormone-dependent breast cancers. Hence, drugs able to impede the emergence of an active folding of ERα have been used for a long time as a first line therapeutic strategy. Aromatase inhibitors that block estradiol synthesis and/or antiestrogens that compete with hormone binding to the receptor are routinely prescribed. Unfortunately, emergence of tumor resistance almost invariably results from currently used antihormonal approaches. One may anticipate that a multi-target strategy affecting key regulatory domains distinct from ligand binding pocket of ERα may help to circumvent this problem. To reach this goal, the synthesis of peptides that may specifically inhibit intra- or inter-molecular interactions has been proposed. This paper describes functional motifs potentially suitable for the design of such antagonists. Activity of available peptidic and non-peptidic mimics of these motifs is also reviewed. © 2011 Bentham Science Publishers.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Activation of the estrogen receptor alpha (ERα) is of prime importance for the development of hormone-dependent breast cancers. Hence, drugs able to impede the emergence of an active folding of ERα have been used for a long time as a first line therapeutic strategy. Aromatase inhibitors that block estradiol synthesis and/or antiestrogens that compete with hormone binding to the receptor are routinely prescribed. Unfortunately, emergence of tumor resistance almost invariably results from currently used antihormonal approaches. One may anticipate that a multi-target strategy affecting key regulatory domains distinct from ligand binding pocket of ERα may help to circumvent this problem. To reach this goal, the synthesis of peptides that may specifically inhibit intra- or inter-molecular interactions has been proposed. This paper describes functional motifs potentially suitable for the design of such antagonists. Activity of available peptidic and non-peptidic mimics of these motifs is also reviewed. © 2011 Bentham Science Publishers. |
Lack of sufficient information on the specificity and selectivity of commercial phytoestrogens preparations for therapeutic purposes Article de journal G Leclercq; P De Cremoux; P This; Y Jacquot Maturitas, 68 (1), p. 56–64, 2011. @article{Leclercq:2011a, title = {Lack of sufficient information on the specificity and selectivity of commercial phytoestrogens preparations for therapeutic purposes}, author = {G Leclercq and P De Cremoux and P This and Y Jacquot}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-78650589344&doi=10.1016%2fj.maturitas.2010.10.003&partnerID=40&md5=10e3529d36119c755129a4edee2491bd}, doi = {10.1016/j.maturitas.2010.10.003}, year = {2011}, date = {2011-01-01}, journal = {Maturitas}, volume = {68}, number = {1}, pages = {56--64}, abstract = {Phytoestrogens (PEs) are polyphenols of plant origin among which flavones, flavanones, isoflavones, coumarins, chalcones, lignans and stilbenes are the best representatives. By interacting with specific residues of the estradiol-binding pocket of estrogen receptors (ERs), they induce estrogenic responses, supporting the concept that they could be of benefits against the menopausal disorders due to endogenous estradiol depletion. According to literature data, PEs target a panel of proteins, suggesting that their effects are not limited to ER-dependent transcription pathways. In this regard, commercial preparations usually contain a mixture of compounds of which nature and concentration are not specified. Such mixtures being freely accessible and escaping thereby medical survey, they could exert unwanted effects, depending on their qualitative and quantitative composition as well as the physiopathological status of the women. This work outlines the necessity to inform consumers of the exact nature of these PEs preparations. Moreover, women who want to take PEs should inform their practitioner to be under strict medical survey. In the case of hormone-dependent cancer antecedents or predispositions, use of PEs is extremely inadvisable. © 2010 Elsevier Ireland Ltd. All rights reserved.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Phytoestrogens (PEs) are polyphenols of plant origin among which flavones, flavanones, isoflavones, coumarins, chalcones, lignans and stilbenes are the best representatives. By interacting with specific residues of the estradiol-binding pocket of estrogen receptors (ERs), they induce estrogenic responses, supporting the concept that they could be of benefits against the menopausal disorders due to endogenous estradiol depletion. According to literature data, PEs target a panel of proteins, suggesting that their effects are not limited to ER-dependent transcription pathways. In this regard, commercial preparations usually contain a mixture of compounds of which nature and concentration are not specified. Such mixtures being freely accessible and escaping thereby medical survey, they could exert unwanted effects, depending on their qualitative and quantitative composition as well as the physiopathological status of the women. This work outlines the necessity to inform consumers of the exact nature of these PEs preparations. Moreover, women who want to take PEs should inform their practitioner to be under strict medical survey. In the case of hormone-dependent cancer antecedents or predispositions, use of PEs is extremely inadvisable. © 2010 Elsevier Ireland Ltd. All rights reserved. |
V Pelekanou; M Kampa; D Gallo; G Notas; M Troullinaki; H Duvillier; Y Jacquot; E N Stathopoulos; E Castanas; G Leclercq Molecular Oncology, 5 (1), p. 36–47, 2011. @article{Pelekanou:2011, title = {The estrogen receptor alpha-derived peptide ERα17p (P295-{T}311) exerts pro-apoptotic actions in breast cancer cells in vitro and in vivo, independently from their ERα status}, author = {V Pelekanou and M Kampa and D Gallo and G Notas and M Troullinaki and H Duvillier and Y Jacquot and E N Stathopoulos and E Castanas and G Leclercq}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-78951477564&doi=10.1016%2fj.molonc.2010.11.001&partnerID=40&md5=9d871a8183b2ebb35cb4bcd29d45c239}, doi = {10.1016/j.molonc.2010.11.001}, year = {2011}, date = {2011-01-01}, journal = {Molecular Oncology}, volume = {5}, number = {1}, pages = {36--47}, abstract = {In recent years, our knowledge on estrogen receptors (ER) has been modified profoundly with the identification and the deciphering of the role of its protein effectors, as well as with the deeper insight of its molecular structure/function dynamics, characteristics associated with its nucleo-cytoplasmic-membrane shuttling properties. Also, significant progress has been made concerning its turn-over and associated final proteasomal degradation processes. These advances could lead in the near future to the design and the synthesis of novel receptor-interacting drugs. Recently, a number of receptor-related peptides acting as specific ER ligands have been identified and extensively studied with respect to their estrogenic/antiestrogenic activities. Among them, ERα17p, a synthetic analog of the P295-T311 sequence of ERα, has been shown to exert pseudo-estrogenic effects by interacting in the close vicinity of its hinge region (BF3 domain). Remarkably, this sequence appears as the epicenter of a number of post-transcriptional modifications as well as of the recruitment of co-regulators, suggesting that it would play a key role in ERα functions. Here, we provide evidence that ERα17p induces apoptosis in ERα-positive (MCF-7, T47D) and -negative (MDA-MB-231, SK-BR-3) breast cancer cells by an ERα-independent membrane mechanism, triggering major pro-apoptotic signaling cascades. Finally, ERα17p induces the regression of breast ERα-negative cancer tumor xenografts, without apparent toxicity, suggesting that it could represent a new attractive tool for the development of future promising therapeutic approaches, and providing a novel insight to ER regulation of cell fate. © 2010 Federation of European Biochemical Societies.}, keywords = {}, pubstate = {published}, tppubtype = {article} } In recent years, our knowledge on estrogen receptors (ER) has been modified profoundly with the identification and the deciphering of the role of its protein effectors, as well as with the deeper insight of its molecular structure/function dynamics, characteristics associated with its nucleo-cytoplasmic-membrane shuttling properties. Also, significant progress has been made concerning its turn-over and associated final proteasomal degradation processes. These advances could lead in the near future to the design and the synthesis of novel receptor-interacting drugs. Recently, a number of receptor-related peptides acting as specific ER ligands have been identified and extensively studied with respect to their estrogenic/antiestrogenic activities. Among them, ERα17p, a synthetic analog of the P295-T311 sequence of ERα, has been shown to exert pseudo-estrogenic effects by interacting in the close vicinity of its hinge region (BF3 domain). Remarkably, this sequence appears as the epicenter of a number of post-transcriptional modifications as well as of the recruitment of co-regulators, suggesting that it would play a key role in ERα functions. Here, we provide evidence that ERα17p induces apoptosis in ERα-positive (MCF-7, T47D) and -negative (MDA-MB-231, SK-BR-3) breast cancer cells by an ERα-independent membrane mechanism, triggering major pro-apoptotic signaling cascades. Finally, ERα17p induces the regression of breast ERα-negative cancer tumor xenografts, without apparent toxicity, suggesting that it could represent a new attractive tool for the development of future promising therapeutic approaches, and providing a novel insight to ER regulation of cell fate. © 2010 Federation of European Biochemical Societies. |
Calmodulin association with the synthetic ERα17p peptide investigated by mass spectrometry Article de journal S Bourgoin-Voillard; F Fournier; C Afonso; Y Jacquot; G Leclercq; J -C Tabet International Journal of Mass Spectrometry, 305 (2-3), p. 87–94, 2011. @article{Bourgoin-Voillard:2011, title = {Calmodulin association with the synthetic ERα17p peptide investigated by mass spectrometry}, author = {S Bourgoin-Voillard and F Fournier and C Afonso and Y Jacquot and G Leclercq and J -C Tabet}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-80051546097&doi=10.1016%2fj.ijms.2010.06.029&partnerID=40&md5=22c5fc2df50bcbe20e295d9ef6a032f9}, doi = {10.1016/j.ijms.2010.06.029}, year = {2011}, date = {2011-01-01}, journal = {International Journal of Mass Spectrometry}, volume = {305}, number = {2-3}, pages = {87--94}, abstract = {Implication of calmodulin (CaM) in breast cancer development has been proposed, justifying the interest for ER/calmodulin interaction. The association of the synthetic peptide ERα17p (H-PLMIKRSKKNSLALSLT-OH), which corresponds to the known ER interaction site of CaM, was investigated. Under physiologically conditions, 1:1 complex formation was observed using an ESI-ITMS instrument. This equimolar complex with CaM was only formed in presence of calcium. The binding of ERα17p to CaM is probably due to presence of four basic residues (K299RSKK303) in its sequence. Its relative binding affinity in solution by ESI-MS was evaluated by performing competitive binding experiments with other peptides more (ERα17pKR: KRSKR) or less basic (ERα17pAA: KRSAA) than ERα17p as well as Melittin (Mel), selected as a reference peptide since it is known to form a high-affinity complex with CaM. Relative affinities of these peptides for CaM were classified in the following decreasing order: Mel > ERα17pKR ∼ ERα17p ERα17pAA. Interestingly, another ion series showing two peptides for one protein was detected. The specificity of this complex not often reported for Melittin is discussed. © 2010 Elsevier B.V.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Implication of calmodulin (CaM) in breast cancer development has been proposed, justifying the interest for ER/calmodulin interaction. The association of the synthetic peptide ERα17p (H-PLMIKRSKKNSLALSLT-OH), which corresponds to the known ER interaction site of CaM, was investigated. Under physiologically conditions, 1:1 complex formation was observed using an ESI-ITMS instrument. This equimolar complex with CaM was only formed in presence of calcium. The binding of ERα17p to CaM is probably due to presence of four basic residues (K299RSKK303) in its sequence. Its relative binding affinity in solution by ESI-MS was evaluated by performing competitive binding experiments with other peptides more (ERα17pKR: KRSKR) or less basic (ERα17pAA: KRSAA) than ERα17p as well as Melittin (Mel), selected as a reference peptide since it is known to form a high-affinity complex with CaM. Relative affinities of these peptides for CaM were classified in the following decreasing order: Mel > ERα17pKR ∼ ERα17p ERα17pAA. Interestingly, another ion series showing two peptides for one protein was detected. The specificity of this complex not often reported for Melittin is discussed. © 2010 Elsevier B.V. |
A critical view of the effects of phytoestrogens on hot flashes and breast cancer risk Article de journal P This; P De Cremoux; G Leclercq; Y Jacquot Maturitas, 70 (3), p. 222–226, 2011. @article{This:2011, title = {A critical view of the effects of phytoestrogens on hot flashes and breast cancer risk}, author = {P This and P De Cremoux and G Leclercq and Y Jacquot}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-80054098726&doi=10.1016%2fj.maturitas.2011.07.001&partnerID=40&md5=6cb342d426744a9f5000de0371677486}, doi = {10.1016/j.maturitas.2011.07.001}, year = {2011}, date = {2011-01-01}, journal = {Maturitas}, volume = {70}, number = {3}, pages = {222--226}, abstract = {The increased risk of breast cancer recently observed with some specific estro-progestin associations has raised concerns about the harmful effects of menopausal hormone replacement therapy (HRT). It has been proposed that phytoestrogens (PEs), which have a similar chemical structure to estrogens, could be used as HRT. The main selling points of these preparations concern the management of hot flashes and their potential beneficial effects on breast tissue. In this review, we will address the effects of PE on hot flashes and breast cancer risk as well as the questions raised on a chemical point of view. We conclude that the efficacy of a PE rich diet or nutritional supplements is not clearly established. The use of PE as an alternative for HRT cannot be advocated for now, due to insufficient and conflicting data on efficacy and safety. Moreover, due to the hormone dependence of breast cancer, PE use must be contraindicated in breast cancer survivors. © 2011 Elsevier Ireland Ltd. All rights reserved.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The increased risk of breast cancer recently observed with some specific estro-progestin associations has raised concerns about the harmful effects of menopausal hormone replacement therapy (HRT). It has been proposed that phytoestrogens (PEs), which have a similar chemical structure to estrogens, could be used as HRT. The main selling points of these preparations concern the management of hot flashes and their potential beneficial effects on breast tissue. In this review, we will address the effects of PE on hot flashes and breast cancer risk as well as the questions raised on a chemical point of view. We conclude that the efficacy of a PE rich diet or nutritional supplements is not clearly established. The use of PE as an alternative for HRT cannot be advocated for now, due to insufficient and conflicting data on efficacy and safety. Moreover, due to the hormone dependence of breast cancer, PE use must be contraindicated in breast cancer survivors. © 2011 Elsevier Ireland Ltd. All rights reserved. |
ERα17p, an ERα P 295-Ŧ 311 fragment, modifies the migration of breast cancer cells, through actin cytoskeleton rearrangements Article de journal M Kampa; V Pelekanou; D Gallo; G Notas; M Troullinaki; I Pediaditakis; I Charalampopoulos; Y Jacquot; G Leclercq; E Castanas Journal of Cellular Biochemistry, 112 (12), p. 3786–3796, 2011. @article{Kampa:2011, title = {ERα17p, an ERα P 295-{T} 311 fragment, modifies the migration of breast cancer cells, through actin cytoskeleton rearrangements}, author = {M Kampa and V Pelekanou and D Gallo and G Notas and M Troullinaki and I Pediaditakis and I Charalampopoulos and Y Jacquot and G Leclercq and E Castanas}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-80055015773&doi=10.1002%2fjcb.23309&partnerID=40&md5=e1e647d93aaf3a20ba97bc52c0dc380c}, doi = {10.1002/jcb.23309}, year = {2011}, date = {2011-01-01}, journal = {Journal of Cellular Biochemistry}, volume = {112}, number = {12}, pages = {3786--3796}, abstract = {Recently, our knowledge on estrogen receptor alpha (ERα) functions and fate has progressed: ERα enters in repeated transcription-modulating cycles (nucleus/cytoplasm/membrane trafficking processes and proteasomal degradation) that are governed by specific protein-protein interactions. Receptor fragments, especially those resulting from the proteolysis of its ligand binding domain, as well as corresponding synthetic peptides, have been studied with respect to their estrogenic/antiestrogenic potency. A peptide, corresponding to the human ERα P 295-T 311 sequence (ERα17p) has been shown to alter breast cancer cell fate, triggering proliferation, or apoptosis. The aim of this work was to explore the effect of ERα17p on breast cancer cell migration and actin cytoskeleton dynamics and further analyze the mechanism of its membrane action. We show that ERα17p increases (MCF-7 and SK-BR-3 cells) or decreases (T47D and MDA-MB-231 cells) migration of breast cancer cells, in an ERα-independent manner, by mechanism(s) depending on Rho/ROCK and PI3K/Akt signaling pathways. Moreover, the peptide enhances the association of both estrogens and androgens to membranes and modifies cell migration, induced by E 2-BSA. Additionally, initial evidence of a possible agonistic action of the peptide on GPR30 is also provided. ERα17p can be considered as a cell migration-modulator and could therefore constitute a therapeutic challenge, even in anti-estrogen-resistant tumors. © 2011 Wiley Periodicals, Inc.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Recently, our knowledge on estrogen receptor alpha (ERα) functions and fate has progressed: ERα enters in repeated transcription-modulating cycles (nucleus/cytoplasm/membrane trafficking processes and proteasomal degradation) that are governed by specific protein-protein interactions. Receptor fragments, especially those resulting from the proteolysis of its ligand binding domain, as well as corresponding synthetic peptides, have been studied with respect to their estrogenic/antiestrogenic potency. A peptide, corresponding to the human ERα P 295-T 311 sequence (ERα17p) has been shown to alter breast cancer cell fate, triggering proliferation, or apoptosis. The aim of this work was to explore the effect of ERα17p on breast cancer cell migration and actin cytoskeleton dynamics and further analyze the mechanism of its membrane action. We show that ERα17p increases (MCF-7 and SK-BR-3 cells) or decreases (T47D and MDA-MB-231 cells) migration of breast cancer cells, in an ERα-independent manner, by mechanism(s) depending on Rho/ROCK and PI3K/Akt signaling pathways. Moreover, the peptide enhances the association of both estrogens and androgens to membranes and modifies cell migration, induced by E 2-BSA. Additionally, initial evidence of a possible agonistic action of the peptide on GPR30 is also provided. ERα17p can be considered as a cell migration-modulator and could therefore constitute a therapeutic challenge, even in anti-estrogen-resistant tumors. © 2011 Wiley Periodicals, Inc. |
Different membrane behaviour and cellular uptake of three basic arginine-rich peptides Article de journal A Walrant; I Correia; C -Y Jiao; O Lequin; E H Bent; N Goasdoué; C Lacombe; G Chassaing; S Sagan; I D Alves Biochimica et Biophysica Acta - Biomembranes, 1808 (1), p. 382–393, 2011. @article{Walrant:2011, title = {Different membrane behaviour and cellular uptake of three basic arginine-rich peptides}, author = {A Walrant and I Correia and C -Y Jiao and O Lequin and E H Bent and N Goasdou\'{e} and C Lacombe and G Chassaing and S Sagan and I D Alves}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-78649801857&doi=10.1016%2fj.bbamem.2010.09.009&partnerID=40&md5=ec9f20d0ebf1ec5af399b6f23b1ad695}, doi = {10.1016/j.bbamem.2010.09.009}, year = {2011}, date = {2011-01-01}, journal = {Biochimica et Biophysica Acta - Biomembranes}, volume = {1808}, number = {1}, pages = {382--393}, abstract = {Cell penetrating peptides (CPPs) are peptides displaying the ability to cross cell membranes and transport cargo molecules inside cells. Several uptake mechanisms (endocytic or direct translocation through the membrane) are being considered, but the interaction between the CPP and the cell membrane is certainly a preliminary key point to the entry of the peptide into the cell. In this study, we used three basic peptides: RL9 (RRLLRRLRR-NH2), RW9 (RRWWRRWRR-NH2) and R9 (RRRRRRRRR-NH2). While RW9 and R9 were internalised into wild type Chinese Hamster Ovary cells (CHO) and glycosaminoglycan-deficient CHO cells, at 4 °C and 37 °C, RL9 was not internalised into CHO cells. To better understand the differences between RW9, R9 and RL9 in terms of uptake, we studied the interaction of these peptides with model lipid membranes. The effect of the three peptides on the thermotropic phase behaviour of a zwitterionic lipid (DMPC) and an anionic lipid (DMPG) was investigated with differential scanning calorimetry (DSC). The presence of negative charges on the lipid headgroups appeared to be essential to trigger the peptide/lipid interaction. RW9 and R9 disturbed the main phase transition of DMPG, whereas RL9 did not induce significant effects. Isothermal titration calorimetry (ITC) allowed us to study the binding of these peptides to large unilamellar vesicles (LUVs). RW9 and R9 proved to have about ten fold more affinity for DSPG LUVs than RL9. With circular dichroism (CD) and NMR spectroscopy, the secondary structure of RL9, RW9 and R9 in aqueous buffer or lipid/detergent conditions was investigated. Additionally, we tested the antimicrobial activity of these peptides against Escherichia coli and Staphylococcus aureus, as CPPs and antimicrobial peptides are known to share several common characteristics. Only RW9 was found to be mildly bacteriostatic against E. coli. These studies helped us to get a better understanding as to why R9 and RW9 are able to cross the cell membrane while RL9 remains bound to the surface without entering the cell. © 2010 Elsevier B.V.All rights reserved.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Cell penetrating peptides (CPPs) are peptides displaying the ability to cross cell membranes and transport cargo molecules inside cells. Several uptake mechanisms (endocytic or direct translocation through the membrane) are being considered, but the interaction between the CPP and the cell membrane is certainly a preliminary key point to the entry of the peptide into the cell. In this study, we used three basic peptides: RL9 (RRLLRRLRR-NH2), RW9 (RRWWRRWRR-NH2) and R9 (RRRRRRRRR-NH2). While RW9 and R9 were internalised into wild type Chinese Hamster Ovary cells (CHO) and glycosaminoglycan-deficient CHO cells, at 4 °C and 37 °C, RL9 was not internalised into CHO cells. To better understand the differences between RW9, R9 and RL9 in terms of uptake, we studied the interaction of these peptides with model lipid membranes. The effect of the three peptides on the thermotropic phase behaviour of a zwitterionic lipid (DMPC) and an anionic lipid (DMPG) was investigated with differential scanning calorimetry (DSC). The presence of negative charges on the lipid headgroups appeared to be essential to trigger the peptide/lipid interaction. RW9 and R9 disturbed the main phase transition of DMPG, whereas RL9 did not induce significant effects. Isothermal titration calorimetry (ITC) allowed us to study the binding of these peptides to large unilamellar vesicles (LUVs). RW9 and R9 proved to have about ten fold more affinity for DSPG LUVs than RL9. With circular dichroism (CD) and NMR spectroscopy, the secondary structure of RL9, RW9 and R9 in aqueous buffer or lipid/detergent conditions was investigated. Additionally, we tested the antimicrobial activity of these peptides against Escherichia coli and Staphylococcus aureus, as CPPs and antimicrobial peptides are known to share several common characteristics. Only RW9 was found to be mildly bacteriostatic against E. coli. These studies helped us to get a better understanding as to why R9 and RW9 are able to cross the cell membrane while RL9 remains bound to the surface without entering the cell. © 2010 Elsevier B.V.All rights reserved. |
Subcellular IR imaging of a metal-carbonyl moiety using photothermally induced resonance Article de journal C Policar; J B Waern; M -A Plamont; S Clède; C Mayet; R Prazeres; J -M Ortega; A Vessières; A Dazzi Angewandte Chemie - International Edition, 50 (4), p. 860–864, 2011. @article{Policar:2011, title = {Subcellular IR imaging of a metal-carbonyl moiety using photothermally induced resonance}, author = {C Policar and J B Waern and M -A Plamont and S Cl\`{e}de and C Mayet and R Prazeres and J -M Ortega and A Vessi\`{e}res and A Dazzi}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-78650905440&doi=10.1002%2fanie.201003161&partnerID=40&md5=68f3379717f4b84ab8336cdb50461a5f}, doi = {10.1002/anie.201003161}, year = {2011}, date = {2011-01-01}, journal = {Angewandte Chemie - International Edition}, volume = {50}, number = {4}, pages = {860--864}, abstract = {Some like it hot! The photothermally induced resonance technique, in which an AFM microscope is coupled to a tunable pulsed IR laser, allows IR mapping and gives access to local IR spectra at the subcellular level. A metal-carbonyl compound was internalized in cells and detected in the cell nucleus thanks to its IR signature. The local IR spectrum at the nucleus showed the characteristic IR bands of the Re(CO)3 unit. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Some like it hot! The photothermally induced resonance technique, in which an AFM microscope is coupled to a tunable pulsed IR laser, allows IR mapping and gives access to local IR spectra at the subcellular level. A metal-carbonyl compound was internalized in cells and detected in the cell nucleus thanks to its IR signature. The local IR spectrum at the nucleus showed the characteristic IR bands of the Re(CO)3 unit. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
Proton-coupled electron transfers in biomimetic water bound metal complexes. the electrochemical approach Article de journal E Anxolabéhère-Mallart; C Costentin; C Policar; M Robert; J -M Savéant; A -L Teillout Faraday Discussions, 148 , p. 83–95, 2011. @article{Anxolabehere-Mallart:2011, title = {Proton-coupled electron transfers in biomimetic water bound metal complexes. the electrochemical approach}, author = {E Anxolab\'{e}h\`{e}re-Mallart and C Costentin and C Policar and M Robert and J -M Sav\'{e}ant and A -L Teillout}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-79952268478&doi=10.1039%2fc004276e&partnerID=40&md5=24036168d6b9ca482d1b9f949b3a5995}, doi = {10.1039/c004276e}, year = {2011}, date = {2011-01-01}, journal = {Faraday Discussions}, volume = {148}, pages = {83--95}, abstract = {Water-bound metal (M) complexes play a central role in the catalytic centers of natural systems such as Photosystem II (PSII), superoxide dismutase, cytochrome c oxidase and others. In these systems, electron transfer reactions involving the metal center are coupled to proton transfers. Besides its fundamental interest, comprehension of these reactions and of possible bio-inspired catalytic devices is an additional motivation for studying the coupling between proton and electron transfer (proton-coupled electron transfers, PCET), starting with an aqua-MII/hydroxo-MIII couple, and going to higher oxidation degrees as in the case of PSII (hydroxo-MIII/oxo-MIV couple). Factors that determine the occurrence of the stepwise and concerted pathways are recalled from the illustrating example of a recently described mononuclear osmium complex, thus opening perspectives for further studies of the biomimicking complex. PCET in a mononuclear aqua/hydroxo manganese couple was then studied using the electrochemical approach. © 2011 The Royal Society of Chemistry.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Water-bound metal (M) complexes play a central role in the catalytic centers of natural systems such as Photosystem II (PSII), superoxide dismutase, cytochrome c oxidase and others. In these systems, electron transfer reactions involving the metal center are coupled to proton transfers. Besides its fundamental interest, comprehension of these reactions and of possible bio-inspired catalytic devices is an additional motivation for studying the coupling between proton and electron transfer (proton-coupled electron transfers, PCET), starting with an aqua-MII/hydroxo-MIII couple, and going to higher oxidation degrees as in the case of PSII (hydroxo-MIII/oxo-MIV couple). Factors that determine the occurrence of the stepwise and concerted pathways are recalled from the illustrating example of a recently described mononuclear osmium complex, thus opening perspectives for further studies of the biomimicking complex. PCET in a mononuclear aqua/hydroxo manganese couple was then studied using the electrochemical approach. © 2011 The Royal Society of Chemistry. |
Intrinsically fluorescent glycoligands to study metal selectivity Article de journal L Garcia; S Maisonneuve; J Oudinet-Sin Marcu; R Guillot; F Lambert; J Xie; C Policar Inorganic Chemistry, 50 (22), p. 11353–11362, 2011. @article{Garcia:2011, title = {Intrinsically fluorescent glycoligands to study metal selectivity}, author = {L Garcia and S Maisonneuve and J Oudinet-Sin Marcu and R Guillot and F Lambert and J Xie and C Policar}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-81255195281&doi=10.1021%2fic200897v&partnerID=40&md5=2d82616942d473b2774c71363fb8ff6a}, doi = {10.1021/ic200897v}, year = {2011}, date = {2011-01-01}, journal = {Inorganic Chemistry}, volume = {50}, number = {22}, pages = {11353--11362}, abstract = {Glycoligands are a versatile family of ligands centered on a sugar platform and functionalized by Lewis bases. In this article, pentofuranoses were appended with the fluoroionophores 4-(pyridin-2′-yl)-1,2,3-triazol-1-yl and 4-(2′,1′,3′-benzothiadiazol-4′-yl)-1,2,3-triazol-1- yl using the "click-like" cycloaddition [2 + 3] of Huisgen catalyzed by copper(I). Their fluorescence properties were used to study metal cation complexation. A possible selective functionalization of furanoscaffolds allows the synthesis of "mixed" glycoligands with the successive insertion of these different fluoroionophores. The metal selectivity and the chelating behavior of these six resulting intrinsically fluorescent glycoligands were investigated. The change in the configuration at the carbon C3 of furanose did not influence either the metal selectivity or the binding constants. However, different selectivities and binding constants were found to depend on the nature of the fluoroionophore moieties. Overall, the triazolylbenzothiadiazolyl chelating group was shown to be less efficient than the triazolylpyridyl claw for complexation. Interestingly enough, the triazolylbenzothiadiazolyl claw, which fluoresces in the visible range, did not interfere in the binding and selectivity of the more efficient triazolylpyridyl claw. This study suggests that the triazolylbenzothiadiazolyl moiety could be used as an adequate fluorescent reporter to qualitatively monitor complexation of other moieties. © 2011 American Chemical Society.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Glycoligands are a versatile family of ligands centered on a sugar platform and functionalized by Lewis bases. In this article, pentofuranoses were appended with the fluoroionophores 4-(pyridin-2′-yl)-1,2,3-triazol-1-yl and 4-(2′,1′,3′-benzothiadiazol-4′-yl)-1,2,3-triazol-1- yl using the "click-like" cycloaddition [2 + 3] of Huisgen catalyzed by copper(I). Their fluorescence properties were used to study metal cation complexation. A possible selective functionalization of furanoscaffolds allows the synthesis of "mixed" glycoligands with the successive insertion of these different fluoroionophores. The metal selectivity and the chelating behavior of these six resulting intrinsically fluorescent glycoligands were investigated. The change in the configuration at the carbon C3 of furanose did not influence either the metal selectivity or the binding constants. However, different selectivities and binding constants were found to depend on the nature of the fluoroionophore moieties. Overall, the triazolylbenzothiadiazolyl chelating group was shown to be less efficient than the triazolylpyridyl claw for complexation. Interestingly enough, the triazolylbenzothiadiazolyl claw, which fluoresces in the visible range, did not interfere in the binding and selectivity of the more efficient triazolylpyridyl claw. This study suggests that the triazolylbenzothiadiazolyl moiety could be used as an adequate fluorescent reporter to qualitatively monitor complexation of other moieties. © 2011 American Chemical Society. |
Relative helix-helix conformations in branched aromatic oligoamide foldamers Article de journal N Delsuc; S Massip; J -M Léger; B Kauffmann; I Huc Journal of the American Chemical Society, 133 (9), p. 3165–3172, 2011. @article{Delsuc:2011, title = {Relative helix-helix conformations in branched aromatic oligoamide foldamers}, author = {N Delsuc and S Massip and J -M L\'{e}ger and B Kauffmann and I Huc}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-79952263733&doi=10.1021%2fja110677a&partnerID=40&md5=36f1e84ade60bac4aee1c82b34b28b99}, doi = {10.1021/ja110677a}, year = {2011}, date = {2011-01-01}, journal = {Journal of the American Chemical Society}, volume = {133}, number = {9}, pages = {3165--3172}, abstract = {The de novo design and synthesis of large and well-organized, tertiary-like, α-peptidic folded architectures is difficult because it relies on multiple cooperative interactions within and between secondary folded motifs of relatively weak intrinsic stability. The very stable helical structures of oligoamides of 8-amino-2-quinoline carboxylic acid offer a way to circumvent this difficulty thanks to their ability to fold into predictable and stable secondary motifs. Branched architectures comprised of two pairs of tetrameric (1), pentameric (2), or octameric (3) oligomers connected via an ethylene glycol spacer were designed and synthesized. The short spacer holds two helices in close proximity, thus enabling interactions between them. Degrees of freedom allowed in the system are well-defined: the relative P or M handedness of the two helices; the relative orientation of the helix axes; and the gauche or anti conformation of the ethylene spacer. Investigating the structures of 1-3 in the solid state and in solution allowed a detailed picture to be drawn of their conformational preferences and dynamics. The high variability of the solid state structures provides many snapshots of possible solution conformations. Helix-helix handedness communication was evidenced and shown to depend both on solvent and on a defined set of side chains at the helix-helix interface. Interdigitation of the side chains was found to restrict free rotation about the ethylene spacer. One solid state structure shows a high level of symmetry and provides a firm basis to further design specific side chain/side chain directional interactions. © 2011 American Chemical Society.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The de novo design and synthesis of large and well-organized, tertiary-like, α-peptidic folded architectures is difficult because it relies on multiple cooperative interactions within and between secondary folded motifs of relatively weak intrinsic stability. The very stable helical structures of oligoamides of 8-amino-2-quinoline carboxylic acid offer a way to circumvent this difficulty thanks to their ability to fold into predictable and stable secondary motifs. Branched architectures comprised of two pairs of tetrameric (1), pentameric (2), or octameric (3) oligomers connected via an ethylene glycol spacer were designed and synthesized. The short spacer holds two helices in close proximity, thus enabling interactions between them. Degrees of freedom allowed in the system are well-defined: the relative P or M handedness of the two helices; the relative orientation of the helix axes; and the gauche or anti conformation of the ethylene spacer. Investigating the structures of 1-3 in the solid state and in solution allowed a detailed picture to be drawn of their conformational preferences and dynamics. The high variability of the solid state structures provides many snapshots of possible solution conformations. Helix-helix handedness communication was evidenced and shown to depend both on solvent and on a defined set of side chains at the helix-helix interface. Interdigitation of the side chains was found to restrict free rotation about the ethylene spacer. One solid state structure shows a high level of symmetry and provides a firm basis to further design specific side chain/side chain directional interactions. © 2011 American Chemical Society. |
The design, synthesis and photochemical study of a biomimetic cyclodextrin model of Photoactive Yellow Protein (PYP) Article de journal C Loukou; P Changenet-Barret; M -N Rager; P Plaza; M M Martin; J -M Mallet Organic and Biomolecular Chemistry, 9 (7), p. 2209–2218, 2011. @article{Loukou:2011, title = {The design, synthesis and photochemical study of a biomimetic cyclodextrin model of Photoactive Yellow Protein (PYP)}, author = {C Loukou and P Changenet-Barret and M -N Rager and P Plaza and M M Martin and J -M Mallet}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-79952761242&doi=10.1039%2fc0ob00646g&partnerID=40&md5=16e7af6da6d3fc72f489076b2bcc5bad}, doi = {10.1039/c0ob00646g}, year = {2011}, date = {2011-01-01}, journal = {Organic and Biomolecular Chemistry}, volume = {9}, number = {7}, pages = {2209--2218}, abstract = {The design, synthesis and study of the photophysical and photochemical properties of the first biomimetic cyclodextrin (CD) model of photoactive yellow protein (PYP) are described. This model bears a deprotonated trans-p-coumaric acid chromophore, covalently linked via a cysteine moiety to a permethylated 6-monoamino β-CD. NMR and UV/Visible spectroscopy studies showed the formation of strong self-inclusion complexes in water at basic pH. Steady-state photolysis demonstrated that, unlike the free chromophore in solution, excitation of the model molecule leads to the formation of a photoproduct identified as the cis isomer by NMR spectroscopy. These observations provide evidence that the restricted CD cavity offers a promising framework for the design of biomimetic models of the PYP hydrophobic pocket. © 2011 The Royal Society of Chemistry.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The design, synthesis and study of the photophysical and photochemical properties of the first biomimetic cyclodextrin (CD) model of photoactive yellow protein (PYP) are described. This model bears a deprotonated trans-p-coumaric acid chromophore, covalently linked via a cysteine moiety to a permethylated 6-monoamino β-CD. NMR and UV/Visible spectroscopy studies showed the formation of strong self-inclusion complexes in water at basic pH. Steady-state photolysis demonstrated that, unlike the free chromophore in solution, excitation of the model molecule leads to the formation of a photoproduct identified as the cis isomer by NMR spectroscopy. These observations provide evidence that the restricted CD cavity offers a promising framework for the design of biomimetic models of the PYP hydrophobic pocket. © 2011 The Royal Society of Chemistry. |
Synthesis of cross-reactive carbohydrate determinants fragments as tools for in vitro allergy diagnosis Article de journal M Collot; I B H Wilson; M Bublin; K Hoffmann-Sommergruber; J -M Mallet Bioorganic and Medicinal Chemistry, 19 (3), p. 1306–1320, 2011. @article{Collot:2011, title = {Synthesis of cross-reactive carbohydrate determinants fragments as tools for in vitro allergy diagnosis}, author = {M Collot and I B H Wilson and M Bublin and K Hoffmann-Sommergruber and J -M Mallet}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-79551501860&doi=10.1016%2fj.bmc.2010.12.001&partnerID=40&md5=f19cb60b8f90daa2350dbc26ee709c33}, doi = {10.1016/j.bmc.2010.12.001}, year = {2011}, date = {2011-01-01}, journal = {Bioorganic and Medicinal Chemistry}, volume = {19}, number = {3}, pages = {1306--1320}, abstract = {Four biotinylated tri and tetrasaccharide fragments of plant and invertebrate N-glycans were synthesized using methyl tert-butyl phenyl (MBP) thioglycosides donors in order to evaluate their involvement in cross-allergies as cross-reactive carbohydrate determinants (CCDs). Various levels of reactivity to anti-bee and anti-HRP antibodies and with sera from allergic patients were observed when the conjugates were coated on streptavidin microplates. The results showed the potential utility of these xylosylated and fucosylated oligosaccharide fragments in determining CCD antibody epitopes. © 2010 Elsevier Ltd. All rights reserved.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Four biotinylated tri and tetrasaccharide fragments of plant and invertebrate N-glycans were synthesized using methyl tert-butyl phenyl (MBP) thioglycosides donors in order to evaluate their involvement in cross-allergies as cross-reactive carbohydrate determinants (CCDs). Various levels of reactivity to anti-bee and anti-HRP antibodies and with sera from allergic patients were observed when the conjugates were coated on streptavidin microplates. The results showed the potential utility of these xylosylated and fucosylated oligosaccharide fragments in determining CCD antibody epitopes. © 2010 Elsevier Ltd. All rights reserved. |
Amphiphilic behavior and membrane solubility of a dicholesteryl- cyclodextrin Article de journal A Klaus; C Fajolles; M Bauer; M Collot; J -M Mallet; J Daillant Langmuir, 27 (12), p. 7580–7586, 2011. @article{Klaus:2011, title = {Amphiphilic behavior and membrane solubility of a dicholesteryl- cyclodextrin}, author = {A Klaus and C Fajolles and M Bauer and M Collot and J -M Mallet and J Daillant}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-79959203005&doi=10.1021%2fla200863c&partnerID=40&md5=88de5707df7aea36286325960211304f}, doi = {10.1021/la200863c}, year = {2011}, date = {2011-01-01}, journal = {Langmuir}, volume = {27}, number = {12}, pages = {7580--7586}, abstract = {Amphiphilic cyclodextrins (CDs) are good candidates to functionalize natural membranes as well as synthetic vesicles. In this paper, we provide a full description of the interfacial behavior of pure 6I,6IV-(β-cholesteryl) succinylamido-6I,6IV-(6-deoxy-per-(2,3,6-O-methyl))cycloheptaose (TBdSC) and how it inserts in dipalmitoyl-l-α-phosphatidylcholine (DPPC) monolayers as a membrane model. Langmuir isotherms of pure TBdSC suggest a reorganization upon compression, which could be clarified using X-ray reflectivity. The CD head can adjust its conformation to the available area per molecule. A compatible model involving a rotation around a horizontal axis defined by the two selectively substituted glucose units is proposed. The in-plane structure is characterized at all scales by Brewster angle microscopy (BAM) on the water surface and atomic force microscopy (AFM) on monolayers deposited on solid substrates. The same tools are used for its mixtures with DPPC. We show in particular that TBdSC seems to be soluble in the liquid-expanded DPPC. However, phase segregation occurs at higher pressure, allowing for sequentially liquid-condensed DPPC and high-pressure conformation of TBdSC. This gives rise to a remarkable contrast inversion in both imaging methods. © 2011 American Chemical Society.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Amphiphilic cyclodextrins (CDs) are good candidates to functionalize natural membranes as well as synthetic vesicles. In this paper, we provide a full description of the interfacial behavior of pure 6I,6IV-(β-cholesteryl) succinylamido-6I,6IV-(6-deoxy-per-(2,3,6-O-methyl))cycloheptaose (TBdSC) and how it inserts in dipalmitoyl-l-α-phosphatidylcholine (DPPC) monolayers as a membrane model. Langmuir isotherms of pure TBdSC suggest a reorganization upon compression, which could be clarified using X-ray reflectivity. The CD head can adjust its conformation to the available area per molecule. A compatible model involving a rotation around a horizontal axis defined by the two selectively substituted glucose units is proposed. The in-plane structure is characterized at all scales by Brewster angle microscopy (BAM) on the water surface and atomic force microscopy (AFM) on monolayers deposited on solid substrates. The same tools are used for its mixtures with DPPC. We show in particular that TBdSC seems to be soluble in the liquid-expanded DPPC. However, phase segregation occurs at higher pressure, allowing for sequentially liquid-condensed DPPC and high-pressure conformation of TBdSC. This gives rise to a remarkable contrast inversion in both imaging methods. © 2011 American Chemical Society. |
Evidences for the Key Role of Hydrogen Bonds in Nucleophilic Aromatic Substitution Reactions Article de journal N Chéron; L El Ka"im; L Grimaud; P Fleurat-Lessard Chemistry - A European Journal, 17 (52), p. 14929-14934, 2011. @article{Cheron:2011, title = {Evidences for the Key Role of Hydrogen Bonds in Nucleophilic Aromatic Substitution Reactions}, author = {N Ch\'{e}ron and L El Ka{"i}m and L Grimaud and P {Fleurat-Lessard}}, doi = {10.1002/chem.201102463}, year = {2011}, date = {2011-01-01}, journal = {Chemistry - A European Journal}, volume = {17}, number = {52}, pages = {14929-14934}, abstract = {The effect of hydrogen bonds on the fate of nucleophilic aromatic substitutions (S NAr) has been studied in silico using a density functional theory approach in the condensed phase. The importance of these hydrogen bonds can explain the "built-in solvation" model of Bunnett concerning intermolecular processes between halogenonitrobenzenes and amines. It is also demonstrated that it can explain experimental results for a multicomponent reaction (the Ugi-Smiles coupling), involving an intramolecular S NAr (the Smiles rearrangement) as the key step of the process. Modeling reveals that when an intramolecular hydrogen bond is present, it lowers the activation barrier of this step and enables the multicomponent reaction to proceed. textcopyright 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The effect of hydrogen bonds on the fate of nucleophilic aromatic substitutions (S NAr) has been studied in silico using a density functional theory approach in the condensed phase. The importance of these hydrogen bonds can explain the "built-in solvation" model of Bunnett concerning intermolecular processes between halogenonitrobenzenes and amines. It is also demonstrated that it can explain experimental results for a multicomponent reaction (the Ugi-Smiles coupling), involving an intramolecular S NAr (the Smiles rearrangement) as the key step of the process. Modeling reveals that when an intramolecular hydrogen bond is present, it lowers the activation barrier of this step and enables the multicomponent reaction to proceed. textcopyright 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
A Density Functional Theory Study of the Nef-Isocyanide Reaction: Mechanism, Influence of Parameters and Scope Article de journal N Chéron; L El Ka"im; L Grimaud; P Fleurat-Lessard Journal of Physical Chemistry A, 115 (35), p. 10106-10112, 2011. @article{Cheron:2011a, title = {A Density Functional Theory Study of the Nef-Isocyanide Reaction: Mechanism, Influence of Parameters and Scope}, author = {N Ch\'{e}ron and L El Ka{"i}m and L Grimaud and P {Fleurat-Lessard}}, doi = {10.1021/jp205909d}, year = {2011}, date = {2011-01-01}, journal = {Journal of Physical Chemistry A}, volume = {115}, number = {35}, pages = {10106-10112}, abstract = {The Nef reaction between isocyanides and acyl chlorides is studied at the M06-2X/6-311+G(d,p) level of theory in toluene. After proving that the reaction follows a concerted mechanism instead of an addition-elimination path, we study the influences of the solvent, the isocyanide, the acyl moiety and the leaving group on the energy profile of the reaction. The calculated data can be rationalized with the pKa of the leaving group, or more generally with the population of the oxygen lone pairs of the acyl moiety. textcopyright 2011 American Chemical Society.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The Nef reaction between isocyanides and acyl chlorides is studied at the M06-2X/6-311+G(d,p) level of theory in toluene. After proving that the reaction follows a concerted mechanism instead of an addition-elimination path, we study the influences of the solvent, the isocyanide, the acyl moiety and the leaving group on the energy profile of the reaction. The calculated data can be rationalized with the pKa of the leaving group, or more generally with the population of the oxygen lone pairs of the acyl moiety. textcopyright 2011 American Chemical Society. |
2010 |
Prolinoamino acids as tools to build bifunctionalized, stable β-turns in water Article de journal C Mothes; M Larregola; J Quancard; N Goasdoué; S Lavielle; G Chassaing; O Lequin; P Karoyan ChemBioChem, 11 (1), p. 55–58, 2010. @article{Mothes:2010, title = {Prolinoamino acids as tools to build bifunctionalized, stable β-turns in water}, author = {C Mothes and M Larregola and J Quancard and N Goasdou\'{e} and S Lavielle and G Chassaing and O Lequin and P Karoyan}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-75649147431&doi=10.1002%2fcbic.200900572&partnerID=40&md5=f83d2fb6456e766acf9c08516116088a}, doi = {10.1002/cbic.200900572}, year = {2010}, date = {2010-01-01}, journal = {ChemBioChem}, volume = {11}, number = {1}, pages = {55--58}, abstract = {(Figure Presented) β-Turn it on: Peptides incorporating cis-3-prolinoamino acids (prolinoleucine or prolinohomotryptophane) and N-methylamino acids (NMePhe/Arg/Lys) have been synthesized to mimic stable β-turns in water (see figure). These 3-substituted prolines are valuable peptidomimetic tools for synthesizing β-turns while keeping the side chain of proteinogenic amino acids. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA.}, keywords = {}, pubstate = {published}, tppubtype = {article} } (Figure Presented) β-Turn it on: Peptides incorporating cis-3-prolinoamino acids (prolinoleucine or prolinohomotryptophane) and N-methylamino acids (NMePhe/Arg/Lys) have been synthesized to mimic stable β-turns in water (see figure). These 3-substituted prolines are valuable peptidomimetic tools for synthesizing β-turns while keeping the side chain of proteinogenic amino acids. © 2010 Wiley-VCH Verlag GmbH & Co. KGaA. |
Comparing lipid photo-cross-linking efficacy of penetratin analogues bearing three different photoprobes: Dithienyl ketone, benzophenone, and trifluoromethylaryldiazirine Article de journal C -Y Jiao; I D Alves; V Point; S Lavielle; S Sagan; G Chassaing Bioconjugate Chemistry, 21 (2), p. 352–359, 2010. @article{Jiao:2010, title = {Comparing lipid photo-cross-linking efficacy of penetratin analogues bearing three different photoprobes: Dithienyl ketone, benzophenone, and trifluoromethylaryldiazirine}, author = {C -Y Jiao and I D Alves and V Point and S Lavielle and S Sagan and G Chassaing}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-77049098162&doi=10.1021%2fbc900466q&partnerID=40&md5=61bb7772a86604849efb4b1d191f5e52}, doi = {10.1021/bc900466q}, year = {2010}, date = {2010-01-01}, journal = {Bioconjugate Chemistry}, volume = {21}, number = {2}, pages = {352--359}, abstract = {Photoactivatable penetratin analogues bearing three different photoprobes, which do not disturb the membranotropic properties of the peptides, have been tested for their photo-cross-linking efficacy in glycerol and lipid media. In the case of glycerol, photo-cross-linking was observed, whereas in the case of SDS (used as a membrane model system), the dynamics of the SDS/penetratin assemblies and the photosensitizer properties of the probes prevented the cross-linking between the peptide and SDS. Bilayers of DMPG were partially photo-cross-linked by the penetratin analogues containing either a benzophenone or a trifluoromethylaryl-diazirine, whereas dithienyl ketone acted exclusively as a photosensitizer. The characterization by MALDI-TOF mass spectrometry of the photoadducts formed after irradiation required basic hydrolysis of DMPG for an efficient capture of the biotinylated peptide analogues with streptavidin-coated magnetic beads. MALDI-TOF analysis of the photoadducts between the photoactivatable penetratin and DMPG allowed an unambiguous identification of the covalent bond formed with the lipids. Altogether, we show herein that the efficacy of the lipid photo-cross-linking depends on the environment, the dynamics of the supramolecular assembly, and the physicochemical properties of the photoprobe. © 2010 American Chemical Society.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Photoactivatable penetratin analogues bearing three different photoprobes, which do not disturb the membranotropic properties of the peptides, have been tested for their photo-cross-linking efficacy in glycerol and lipid media. In the case of glycerol, photo-cross-linking was observed, whereas in the case of SDS (used as a membrane model system), the dynamics of the SDS/penetratin assemblies and the photosensitizer properties of the probes prevented the cross-linking between the peptide and SDS. Bilayers of DMPG were partially photo-cross-linked by the penetratin analogues containing either a benzophenone or a trifluoromethylaryl-diazirine, whereas dithienyl ketone acted exclusively as a photosensitizer. The characterization by MALDI-TOF mass spectrometry of the photoadducts formed after irradiation required basic hydrolysis of DMPG for an efficient capture of the biotinylated peptide analogues with streptavidin-coated magnetic beads. MALDI-TOF analysis of the photoadducts between the photoactivatable penetratin and DMPG allowed an unambiguous identification of the covalent bond formed with the lipids. Altogether, we show herein that the efficacy of the lipid photo-cross-linking depends on the environment, the dynamics of the supramolecular assembly, and the physicochemical properties of the photoprobe. © 2010 American Chemical Society. |
Cell-penetrating peptides with intracellular actin-remodeling activity in malignant fibroblasts Article de journal D Delaroche; F -X Cantrelle; F Subra; C Van Heijenoort; E Guittet; C -Y Jiao; L Blanchoin; G Chassaing; S Lavielle; C Auclair; S Sagan Journal of Biological Chemistry, 285 (10), p. 7712–7721, 2010. @article{Delaroche:2010, title = {Cell-penetrating peptides with intracellular actin-remodeling activity in malignant fibroblasts}, author = {D Delaroche and F -X Cantrelle and F Subra and C Van Heijenoort and E Guittet and C -Y Jiao and L Blanchoin and G Chassaing and S Lavielle and C Auclair and S Sagan}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-77951229473&doi=10.1074%2fjbc.M109.045872&partnerID=40&md5=05b1aaf435ef3ea8dd28c5b7d96c1607}, doi = {10.1074/jbc.M109.045872}, year = {2010}, date = {2010-01-01}, journal = {Journal of Biological Chemistry}, volume = {285}, number = {10}, pages = {7712--7721}, abstract = {Cell-penetrating peptides can cross cell membranes and are commonly seen as biologically inert molecules. However, we found that some cell-penetrating peptides could remodel actin cytoskeleton in oncogene-transformed NIH3T3/EWS-Fli cells. These cells have profound actin disorganization related to their tumoral transformation. These arginine- and/or tryptophanrich peptides could cross cell membrane and induce stress fiber formation in these malignant cells, whereas they had no perceptible effect in non-tumoral fibroblasts. In addition, motility (migration speed, random motility coefficient, wound healing) of the tumor cells could be decreased by the cell-permeant peptides. Although the peptides differently influenced actin polymerization in vitro, they could directly bind monomeric actin as determined by NMR and calorimetry studies. Therefore, cell-penetrating peptides might interact with intracellular protein partners, such as actin. In addition, the fact that they could reverse the tumoral phenotype is of interest for therapeutic purposes. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Cell-penetrating peptides can cross cell membranes and are commonly seen as biologically inert molecules. However, we found that some cell-penetrating peptides could remodel actin cytoskeleton in oncogene-transformed NIH3T3/EWS-Fli cells. These cells have profound actin disorganization related to their tumoral transformation. These arginine- and/or tryptophanrich peptides could cross cell membrane and induce stress fiber formation in these malignant cells, whereas they had no perceptible effect in non-tumoral fibroblasts. In addition, motility (migration speed, random motility coefficient, wound healing) of the tumor cells could be decreased by the cell-permeant peptides. Although the peptides differently influenced actin polymerization in vitro, they could directly bind monomeric actin as determined by NMR and calorimetry studies. Therefore, cell-penetrating peptides might interact with intracellular protein partners, such as actin. In addition, the fact that they could reverse the tumoral phenotype is of interest for therapeutic purposes. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc. |
MALDI-TOF mass spectrometry: A powerful tool to study the internalization of cell-penetrating peptides Article de journal S Aubry; B Aussedat; D Delaroche; C -Y Jiao; G Bolbach; S Lavielle; G Chassaing; S Sagan; F Burlina Biochimica et Biophysica Acta - Biomembranes, 1798 (12), p. 2182–2189, 2010. @article{Aubry:2010, title = {MALDI-TOF mass spectrometry: A powerful tool to study the internalization of cell-penetrating peptides}, author = {S Aubry and B Aussedat and D Delaroche and C -Y Jiao and G Bolbach and S Lavielle and G Chassaing and S Sagan and F Burlina}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-77958137981&doi=10.1016%2fj.bbamem.2009.11.011&partnerID=40&md5=a88feb718ad5b3760513d0779339e018}, doi = {10.1016/j.bbamem.2009.11.011}, year = {2010}, date = {2010-01-01}, journal = {Biochimica et Biophysica Acta - Biomembranes}, volume = {1798}, number = {12}, pages = {2182--2189}, abstract = {This review summarizes the contribution of MALDI-TOF mass spectrometry in the study of cell-penetrating peptide (CPP) internalization in eukaryote cells. This technique was used to measure the efficiency of cell-penetrating peptide cellular uptake and cargo delivery and to analyze carrier and cargo intracellular degradation. The impact of thiol-containing membrane proteins on the internalization of CPP-cargo disulfide conjugates was also evaluated by combining MALDI-TOF MS with simple thiol-specific reactions. This highlighted the formation of cross-linked species to cell-surface proteins that either remained trapped in the cell membrane or led to intracellular delivery. MALDI-TOF MS is thus a powerful tool to dissect CPP internalization mechanisms. © 2009 Elsevier B.V.}, keywords = {}, pubstate = {published}, tppubtype = {article} } This review summarizes the contribution of MALDI-TOF mass spectrometry in the study of cell-penetrating peptide (CPP) internalization in eukaryote cells. This technique was used to measure the efficiency of cell-penetrating peptide cellular uptake and cargo delivery and to analyze carrier and cargo intracellular degradation. The impact of thiol-containing membrane proteins on the internalization of CPP-cargo disulfide conjugates was also evaluated by combining MALDI-TOF MS with simple thiol-specific reactions. This highlighted the formation of cross-linked species to cell-surface proteins that either remained trapped in the cell membrane or led to intracellular delivery. MALDI-TOF MS is thus a powerful tool to dissect CPP internalization mechanisms. © 2009 Elsevier B.V. |
Glycosylated cell-penetrating peptides and their conjugates to a proapoptotic peptide: Preparation by click chemistry and cell viability studies Article de journal L Dutot; P Lécorché; F Burlina; R Marquant; V Point; S Sagan; G Chassaing; J -M Mallet; S Lavielle Journal of Chemical Biology, 3 (2), p. 51–65, 2010. @article{Dutot:2010, title = {Glycosylated cell-penetrating peptides and their conjugates to a proapoptotic peptide: Preparation by click chemistry and cell viability studies}, author = {L Dutot and P L\'{e}corch\'{e} and F Burlina and R Marquant and V Point and S Sagan and G Chassaing and J -M Mallet and S Lavielle}, url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-77954564961&doi=10.1007%2fs12154-009-0031-9&partnerID=40&md5=875cb20c743f24819a3c39ca5059cef6}, doi = {10.1007/s12154-009-0031-9}, year = {2010}, date = {2010-01-01}, journal = {Journal of Chemical Biology}, volume = {3}, number = {2}, pages = {51--65}, abstract = {Cell-penetrating peptides (CPPs), which are usually short basic peptides, are able to cross cell membranes and convey bioactive cargoes inside cells. CPPs have been widely used to deliver inside cells peptides, proteins, and oligonucleotides; however, their entry mechanisms still remain controversial. A major problem concerning CPPs remains their lack of selectivity to target a specific type of cell and/or an intracellular component. We have previously shown that myristoylation of one of these CPPs affected the intracellular distribution of the cargo. We report here on the synthesis of glycosylated analogs of the cell-penetrating peptide (R6/W3): Ac-RRWWRRWRR-NH2. One, two, or three galactose(s), with or without a spacer, were introduced into the sequence of this nonapeptide via a triazole link, the Huisgen reaction being achieved on a solid support. Four of these glycosylated CPPs were coupled via a disulfide bridge to the proapoptotic KLAK peptide, (KLAKLAKKLAKLAK), which alone does not enter into cells. The effect on cell viability and the uptake efficiency of different glycosylated conjugates were studied on CHO cells and were compared to those of the nonglycosylated conjugates: (R6/W3)S-S-KLAK and penetratinS-S-KLAK. We show that glycosylation significantly increases the cell viability of CHO cells compared to the nonglycosylated conjugates and concomitantly decreases the internalization of the KLAK cargo. These results suggest that glycosylation of CPP may be a key point in targeting specific cells. © 2009 Springer-Verlag.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Cell-penetrating peptides (CPPs), which are usually short basic peptides, are able to cross cell membranes and convey bioactive cargoes inside cells. CPPs have been widely used to deliver inside cells peptides, proteins, and oligonucleotides; however, their entry mechanisms still remain controversial. A major problem concerning CPPs remains their lack of selectivity to target a specific type of cell and/or an intracellular component. We have previously shown that myristoylation of one of these CPPs affected the intracellular distribution of the cargo. We report here on the synthesis of glycosylated analogs of the cell-penetrating peptide (R6/W3): Ac-RRWWRRWRR-NH2. One, two, or three galactose(s), with or without a spacer, were introduced into the sequence of this nonapeptide via a triazole link, the Huisgen reaction being achieved on a solid support. Four of these glycosylated CPPs were coupled via a disulfide bridge to the proapoptotic KLAK peptide, (KLAKLAKKLAKLAK), which alone does not enter into cells. The effect on cell viability and the uptake efficiency of different glycosylated conjugates were studied on CHO cells and were compared to those of the nonglycosylated conjugates: (R6/W3)S-S-KLAK and penetratinS-S-KLAK. We show that glycosylation significantly increases the cell viability of CHO cells compared to the nonglycosylated conjugates and concomitantly decreases the internalization of the KLAK cargo. These results suggest that glycosylation of CPP may be a key point in targeting specific cells. © 2009 Springer-Verlag. |