F. Ferrage's ID

Olivier Lequin

Professor at Université Pierre et Marie Curie Deputy Director of Laboratoire des Biomolécules

My research activities are focused on the molecular basis of the interactions involving biomolecules and the design of synthetic molecules able to modulate these interactions. NMR spectroscopy is the main technique of investigation and is used in concert with molecular modelling (protein structure calculation, conformational analysis of small molecules), biochemistry (recombinant protein expression and purification), biophysical and other spectroscopic methods (circular dichroism, fluorescence). The main research axes deal with:
- Conformational studies of bioactive peptides and peptidomimetics
- Interactions of peptides and proteins with membranes
- Protein/ligand interactions
- Structural characterization of synthetic and bioorganic molecules
My teaching activities at Université Pierre et Marie Curie involve NMR spectroscopy for chemists and biochemists, as well as biological chemistry and spectroscopy courses, at the Bachelor (Licence L2, L3) and Master levels (M1, M2). I am responsible of teaching units LC351, LC361, and 3C021.

Keywords

Biomolecular NMR, biochemistry, biophysics,
peptides, peptidomimetics, cell-penetrating peptide, antimicrobial peptide, amyloid peptide, homeoprotein, Engrailed transcription factor

Languages

French: mother tongue, English
Other: German, Latin, Hieroglyphic Egyptian

Education

Olivier Lequin did his undergraduate studies at the Ecole Normale Supérieure de Lyon and Université Claude Bernard in Biochemistry and Chemistry. He received the Agrégation de Biochimie in 1992 and a Master’s degree in 1994. He continued with a PhD in 1997 under the supervision of Prof. Jean-Yves Lallemand (Ecole Polytechnique, Palaiseau, France) working on the NMR structure determination of angiogenins, ribonucleases involved in angiogenesis. In 1998, he got a FEBS postdoctoral fellowship to join Prof. Iain D. Campbell’s group (Department of Biochemistry, University of Oxford, UK), where he worked on the NMR characterization of type III modules of fibronectin involved in matrix assembly and in heparin binding. He was appointed Maître de Conférences in 1999 at Université Pierre et Marie Curie where he worked in collaboration with Gérard Chassaing and Solange Lavielle on structure-activity relationships of peptides and peptidomimetics. Since 2006 he is Professor at Université Pierre et Marie Curie in bioorganic NMR spectroscopy. He is currently Deputy Director of the laboratoire des Biomolécules (UMR 7203 UPMC-ENS-CNRS).

Publications

  • 53- Vahdati L., Fanelli R., Bernadat G., Correia I., Lequin O., Ongeri S., Piarulli U. Synthesis and conformational studies of a stable peptidomimetic beta-hairpin based on a bifunctional diketopiperazine turn inducer. New J. Chem. 2015, DOI 10.1039/C4NJ01437E.
  • 52- Carlier L., Joanne P., Khemtémourian L., Lacombe C., Nicolas P., El Amri C., Lequin O. Investigating the role of GXXXG motifs in helical folding and self-association of plasticins, Gly/Leu-rich antimicrobial peptides. Biophys. Chem. 2015, 196, 40-52.
  • 51- Auberger N., Pisa M.D., Larregola M., Chassaing G., Peroni E., Lavielle S., Papini A.-M., Lequin O., Mallet J.-M. Glaser oxidative coupling on peptides, stabilization of beta-turn structure via a 1,3-butadiyne constraint. Bioorg. Med. Chem. 2014, 22(24), 6924-6932.
  • 50- Caillon L., Duma L., Lequin O., Khemtémourian L. Cholesterol modulates the interaction of the islet amyloid polypeptide with membranes. Molecular Membrane Biology 2014, 31(7-8), 239-249.
  • 49- Kaffy J., Brinet D., Soulier J.-L., Khemtémourian L., Lequin O., Taverna M., Crousse B., Ongeri S. Structure-activity relationships of sugar-based peptidomimetics as modulators of amyloid eta-peptide early oligomerization and fibrillization. Eur. J. Med. Chem. 2014, 86, 752-758.
  • 48- Asgatay S., Champion C., Marloie G., Drujon T., Senamaud-Beaufort C., Ceccaldi A., Rajavelu A., Schambel P., Jeltsch A., Lequin O., Karoyan P., Arimondo P.B., Guianvarc’h D. Synthesis and evaluation of analogues of N-phthaloyl-L-tryptophan RG108 as inhibitors of DNA methyltransferase I. J. Med. Chem. 2014, 57(2), 421-434.
  • 47- Caillon L., Killian J.A., Lequin O., Khemtémourian L. Biophysical investigation of the membrane-disrupting mechanism of the antimicrobial and amyloid-like peptide dermaseptin S9. PLOS One 2013, 8, e75528.
  • 46- Caillon L., Lequin O., Khemtémourian L. Evaluation of membrane models and their composition for islet amyloid polypeptide-membrane aggregation. Biophys. Biochim. Acta-Biomembranes 2013, 1828, 2091-2098.
  • 45- Carlier L., Balayssac S., Cantrelle F.X., Khemtémourian L., Chassaing G., Joliot A., Lequin O. Investigation of homeodomain membrane translocation properties: insights from the structure determination of Engrailed-2 homeodomain in aqueous and membrane-mimetic environments. Biophys. J. 2013, 105, 667-678.
  • 44- Fonvielle M., Le Du M.H., Lequin O., Lecoq A., Jacquet M., Thai R., Dubois S., Grach G., Gondry M., Belin P. Substrate and reaction specificity of Mycobacterium tuberculosis cytochrome P450 CYP121: insights from biochemical studies and crystal structures. J. Biol. Chem. 2013, 288, 17347-17359.
  • 43- Keita M., De Bona R., Dos Santos M., Lequin O., Ongeri S., Milcent T., Crousse B. Access to novel amino trifluoromethyl cyclopropane carboxylic acid derivatives. Tetrahedron 2013, 69, 3308-3315.
  • 42- Caumes C., Delsuc N., Beni Azza R., Correia I., Chemla F., Ferreira F., Carlier L., Perez Luna A., Moumné R., Lequin O., Karoyan P. Homooligomers of substituted prolines and Beta-prolines: syntheses and secondary structure investigation. New J. Chem. 2013, 37, 1312-1319.
  • 41- Mothes C., Caumes C., Guez A., Boullet H., Gendrineau T., Darses S., Delsuc N., Moumné R., Oswald B., Lequin O., Karoyan P. 3-substituted prolines: from synthesis to structural applications, from peptides to foldamers. Molecules 2013, 18(2), 2307-2327.
  • 40- Bechara C., Pallerla M., Zaltsman Y., Burlina F., Alves I.D., Lequin O., Sagan S. Tryptophan within basic peptide sequences triggers glycosaminoglycan-dependent endocytosis. FASEB J. 2013, 27(2), 738-749.
  • 39- Mann S., Eveleigh L., Lequin O., Ploux O. A microplate fluorescence assay for DAPA aminotransferase by detection of the vicinal diamine 7,8-diaminopelargonic acid. Anal Biochem. 2013, 432, 90-96.
  • 38- Carlier L., Haase A.S., Burgos Zepeda M.Y., Dassa E., Lequin O. The C-terminal domain of the Uup protein is a DNA-binding coiled coil motif. J. Struct. Biol. 2012, 180(3), 577-584.
  • 37- Carlier L., Haase S.A.S., Burgos Zepeda M.Y., Dassa E., Lequin O. Secondary structure and NMR resonance assignments of the C-terminal DNA-binding domain of Uup protein. Biomol. NMR Assign. 2012, 6(2), 197-200.
  • 36- Walrant A., Vogel A., Correia I., Lequin O., Olausson B.E.S., Desbat B., Sagan S., Alves I.D. Membrane interactions of two arginine-rich peptides with different cell internalization capacities. Biophys. Biochim. Acta-Biomembranes 2012, 1818, 1755-1763.
  • 35- Carlier L., Byrne C., Miclet E., Bourgoin-Voillard S., Nicaise M., Tabet J.-C., Desmadril M., Leclercq G., Lequin O., Jacquot Y. Biophysical studies of the interaction between calmodulin and the R287-T311 region of human estrogen receptor lpha indicates an atypical binding process. Biochem. Biophys. Res. Comm. 2012, 419(2), 356-361.
  • 34- Halby L., Champion C., Sénamaud-Beaufort C., Ajjan S., Drujon T., Rajavelu A., Ceccaldi A., Jurkowska R., Lequin O., Nelson W.G., Guy A., Jeltsch A., Guianvarc’h D., Ferroud C., Arimondo P.B. Rapid synthesis of new DNMT inhibitors derivatives of procainamide. ChemBioChem 2012, 13(1), 157-165.
  • 33- Dorgeret B., Khemtémourian L., Correia I., Lequin O., Ongeri S. Sugar-based peptidomimetics inhibit amyloid eta-peptide aggregation. Eur. J. Med. Chem. 2011, 46(12), 5959-5969.
  • 32- Augustyniak R., Balayssac S., Ferrage F., Bodenhausen G., Lequin O. 1H, 13C, and 15N resonance assignment of a 114-residue fragment of Engrailed 2 homeoprotein, a partially disordered protein. Biomol. NMR Assign. 2011, 5(2), 229-231.
  • 31- Larregola M., Lequin O., Karoyan P., Guianvarc’h D., Lavielle S. Beta-Amino acids containing peptides and click-cyclized peptide as eta-turn mimics. A comparative study with “conventional” lactam- and disulphide-bridged hexapeptides. J. Pept. Sci. 2011, 17(9), 632-643
  • 30- Augustyniak R., Ferrage F., Paquin R., Lequin O., Bodenhausen G. Methods to determine slow diffusion coefficients of biomolecules. Applications to Engrailed 2, a partially disordered protein. J. Biomol. NMR 2011, 50(3), 209-218.
  • 29- Matheron L., Sachon E., Burlina F., Sagan S., Lequin O., Bolbach G. Sequence-dependent enrichment of a model phosphopeptide: a combined MALDI-TOF and NMR study. Anal. Chem. 2011, 83(8), 3003-3010.
  • 28- Guitot K., Larregola M., Pradan T.K., Vasse J.-L., Lavielle S., Bertus P., Szymoniak J., Lequin O., Karoyan P. The combination of prolinoamino acids and cyclopropylamino acids leads to fully functionalized, stable eta-turns in water. ChemBioChem 2011, 12(7), 1039-1042.
  • 27- Walrant A., Correia I., Jiao C. Y., Lequin O., Bent E. H., Goasdoué N., Lacombe C., Chassaing G., Sagan S., Alves I. D. Different membrane-behaviour and cellular uptake of three basic arginine-rich peptides. Biochim. Biophys. Acta Biomembranes 2011, 1808(1), 382-393.
  • 26- Rose E., Gallo E., Raoul N., Bouché L., Pille A., Caselli A., Lequin O. Chiral “basket handle” binaphthyl porphyrins: synthesis, catalytic epoxidation and NMR conformational studies. J. Porphyrins Phthalocyanines 2010, 14(7), 646-659.
  • 25- Abbassi F., Lequin O., Piesse C., Goasdoué N., Foulon T., Nicolas P., Ladram A. Temporin-SHf, a new type of Phe-rich and hydrophobic ultrashort antimicrobial peptide. J. Biol. Chem. 2010, 285(22), 16880-16892.
  • 24- Mothes C., Larregola M., Quancard J., Goasdoué N., Lavielle S., Chassaing G., Lequin O., Karoyan P. Prolinoamino acids as tools to build bifunctionalized, stable eta-turns in water. ChemBioChem 2010, 11(1), 55-58
  • 23- Dahirel V., Ancian B., Jardat M., Mériguet G.,Turq P., Lequin O. What can be learnt from the comparison of multiscale brownian dynamics simulations, nuclear magnetic resonance and light scattering experiments on charged micelles? Soft Matter 2010, 6(3), 517-525.
  • 22- Méjean A., Mann S., Maldiney T., Vassiliadis G., Lequin O., Ploux O. Evidence that biosynthesis of the neurotoxic alkaloids anatoxin-a and homoanatoxin-a in the cyanobacterium Oscillatoria PCC 6506 occurs on a modular polyketide synthase initiated by L-proline. J. Am. Chem. Soc. 2009, 131(22), 7512-7513.
  • 21- Belin P., Le Du M.H., Fielding A., Lequin O., Jacquet M., Charbonnier J.B., Lecoq A., Thai R., Courçon M., Masson C., Dugave C., Genet R., Pernodet J.L., Gondry M. Identification and structural basis of the reaction catalyzed by CYP121, an essential cytochrome P450 in Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. U.S.A. 2009, 106(18), 7426-7431.
  • 20- Galanth C., Abbassi F., Lequin O., Ayala-Sanmartin J., Ladram A., Nicolas P., Amiche M. Mechanism of antibacterial action of Dermaseptin B2: interplay between helix-hinge-helix structure and membrane curvature strain. Biochemistry 2009, 48(2), 313-327.
  • 19- Abbassi F., Galanth C., Amiche M., Saito K., Piesse C., Zargarian L., Hani K., Nicolas P., Lequin O., Ladram A. Solution structure and model membrane interactions of Temporins-SH, antimicrobial peptides from amphibian skin. A NMR spectroscopy and differential scanning calorimetry study. Biochemistry 2008, 47(40), 10513-10525.
  • 18- Jacquot Y., Broutin I., Miclet E., Nicaise M., Lequin O., Goasdoué N., Joss C., Karoyan P., Desmadril M., Ducruix A., Lavielle S. High affinity Grb2-SH3 domain ligand incorporating Ceta-substituted prolines in a Sos-derived decapeptide. Bioorg. Med. Chem. 2007, 15(3), 1439-1447.
  • 17- Balayssac S., Burlina F., Convert O., Bolbach G., Chassaing G., Lequin O. Comparison of Penetratin and other homeodomain-derived cell-penetrating peptides: interaction in a membrane-mimicking environment and cellular uptake efficiency. Biochemistry 2006, 45, 1408-1420.
  • 16- Lequin O., Ladram A., Chabbert L., Bruston F., Convert O., Vanhoye D., Chassaing G., Nicolas P., Amiche M. Dermaseptin S9, an alpha-helical antimicrobial peptide with a hydrophobic core and cationic termini. Biochemistry 2006, 45, 468-480.
  • 15- Sagan S., Quancard J., Lequin O., Karoyan P., Chassaing G., Lavielle S. Conformational analysis of the C-terminal Gly-Leu-Met-NH2 tripeptide of substance P bound to the NK-1 receptor. Chem. Biol. 2005, 12, 555-565.
  • 14- Karoyan P., Sagan S., Lequin O., Quancard J., Lavielle S., Chassaing G. Substituted prolines: syntheses and applications in structure-activity relationship studies of biologically active peptides. Targets in Heterocyclic Systems 2004, 8, 216-273.
  • 13- Sagan S., Karoyan P., Lequin O., Chassaing G., Lavielle S. N- and Clpha-methylation in biologically active peptides: synthesis, structural and functional aspects. Curr. Med. Chem. 2004, 11, 2799-2822.
  • 12- Baraguey C., Skouri-Panet F., Bontems F., Tardieu A., Chassaing G., Lequin O. Letter to the Editor: 1H, 15N, and 13C resonance assignment of human ammaS-crystallin, a 21 kDa eye-lens protein. J. Biomol. NMR. 2004, 30, 385-386.
  • 11- Quancard J., Karoyan P., Lequin O., Wenger E., Aubry A., Lavielle S., Chassaing G. Prolinoamino acids as a tool to stabilize eta-turns with the side chain of natural amino acids. Tetrahedron Lett. 2004, 45, 623-625.
  • 10- Gao M., Craig D., Lequin O., Campbell I.D., Vogel V., Schulten K. Structure and functional significance of mechanically unfolded fibronectin type III1 intermediates. Proc. Natl. Acad. Sci. U.S.A. 2003, 100, 14784-14789.
  • 9- Zilberberg L., Shinkaruk S., Lequin O., Rousseau B., Hagedorn M., Costa F., Caronzolo D., Balke M., Canron X., Convert O., Laïn G., Gionnet K., Goncalvès M., Bayle M., Bello L., Chassaing G., Deleris G., Bikfalvi A. Structure and inhibitory effects on angiogenesis and tumor development of a new vascular endothelial growth inhibitor. J. Biol. Chem. 2003, 278, 35564-35573.
  • 8- Lequin O., Bruston F., Convert O., Chassaing G., Nicolas P. Helical structure of dermaseptin B2 in a membrane-mimetic environment. Biochemistry 2003, 42, 10311-10323.
  • 7- Quancard J., Karoyan P., Sagan S., Convert O., Lavielle S., Chassaing G., Lequin O. Characterization of the bioactive conformation of the C-terminal tripeptide Gly-Leu-Met-NH2 of substance P using [3-prolinoleucine10]SP analogues. Eur. J. Biochem. 2003, 270, 2869-2878
  • 6- Sagan S., Milcent T., Ponsinet R., Convert O., Tasseau O., Chassaing G., Lavielle S., Lequin O. Structural and biological effects of a Beta2- or Beta3-amino acid insertion in a peptide. Eur. J. Biochem. 2003, 270, 939-949.
  • 5- Sachchidanand, Lequin O., Staunton D., Mulloy B., Forster M.J., Yoshida K., Campbell I.D. Mapping the heparin-binding site on the 13-14F3 fragment of fibronectin. J. Biol. Chem. 2002, 277, 50629-50635.
  • 4- Lequin O., Bolbach G., Frank F., Convert O., Girault-Lagrange S., Chassaing G., Lavielle S., Sagan S. Involvement of the second extracellular loop (E2) of the neurokinin-1 receptor in the binding of substance P. Photoaffinity labeling and modeling studies. J. Biol. Chem. 2002, 277, 22386-22394.
  • 3- Sagan S., Lequin O., Frank F., Convert O., Ayoub M., Lavielle S., Chassaing G. Calpha methylation in molecular recognition. Application to substance P and the two neurokinin-1 receptor binding sites. Eur. J. Biochem. 2001, 268, 2997-3005.
  • 2- Lequin O., Thüring H., Robin M., Lallemand J.-Y. Three-dimensional solution structure of human angiogenin determined by 1H,15N-NMR spectroscopy. Characterization of histidine protonation states and pKa values. Eur. J. Biochem. 1997, 250, 712-726.
  • 1- Lequin O., Albaret C., Bontems F., Spik G., Lallemand J.-Y. Solution structure of bovine angiogenin by 1H nuclear magnetic resonance spectroscopy. Biochemistry 1996, 35, 8870-8880.

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