Chemistry of Amino Acids, Heterocycles, Peptides and Proteins

 Muriel AMBLARD and Jean MARTINEZ

 IBMM - UMR 5247

 15 Avenue de Charles Flahault, 34093 Montpellier

Phone: +33 4 11 75 96 05

           +33 4 11 75 96 01

Emails: muriel.amblard@univ-montp1.fr

            martinez@univ-montp1.fr

Website

The main objectives of this team are the design and the elaboration of new original, active and selective biomolecules with potential applications in therapeutics. This lies on the development of new templates (new privileged structures, bioavailable peptides or proteins, artificial folded structures) and new concepts (new type of delivery system for cellular uptake and BBB permeation, conception of foldamers) for drugs discovery. To achieve the construction of these new molecular systems and to analyze them at the structural level or at the quantification level in complex medium (case of cellular uptake measurement), we develop new methodologies which include chemistry on soluble and solid supports, chemistry under microwaves irradiation, methodology of peptide synthesis, protein analysis, etc. Peptide hormones including neuropeptides of the gastrointestinal tract, G-Protein Coupled Receptors (GPCR) ligands, i.e. gastrin, cholecystokinin, bombesin, neurotensin, ghrelin and enzymes including β-Secretases, Aspartyl-Proteases, Seryl-Proteases constituted the major targets of this team which provided to the scientific community new tools for diagnosis and the understanding of pathological disorders.

Keywords: iup to 5: Peptides, Medicinal Chemistry, Vectorisation, GPCR Ligands, Enzyme inhibitors

Latest publications

• "In vitro inhibition of translation initiation by N,N '-diarylureas-potential anti-cancer agents". S. Denoyelle, T. Chen, L.M. Chen, Y.B. Wang, E. Klosi, J.A. Halperin, B.H. Aktas, M. Chorev. Bioorg. Med. Chem. Lett. 22, 402-409 (2012).
• "Ligands and signaling proteins govern the conformational landscape explored by a G protein-coupled receptor". S. Mary, M. Damian, M. Louet, N. Floquet, J.A. Fehrentz, J. Marie, J. Martinez, J.L. Baneres. Proc. Natl. Acad. Sci. USA 109, 8304-8309 (2012).
• "Selective C-Acylation of 2-Aminoimidazo[1,2-a]pyridine: Application to the Synthesis of Imidazopyridine-Fused [1,3]Diazepinones". N. Masurier, R. Aruta, V. Gaumet, S. Denoyelle, E. Moreau, V. Lisowski, J. Martinez, L.T. Maillard. J. Org. Chem. 77, 3679-3685 (2012).
• "Imidazonaphthyridine systems (part 2): Functionalization of the phenyl ring linked to the pyridine pharmacophore and its replacement by a pyridinone ring produces intriguing differences in cytocidal activity". N. Masurier, E. Debiton, A. Jacquemet, A. Bussiere, J.M. Chezal, A. Ollivier, D. Tetegan, M. Andaloussi, M.J. Galmier, J. Lacroix, D. Canitrot, J.C. Teulade, R.C. Gaudreault, O. Chavignon, E. Moreau. Eur. J. Med. Chem. 52, 137-150 (2012).
• "High constitutive activity is an intrinsic feature of ghrelin receptor protein: a study with a functional monomeric GHS-R1a receptor reconstituted in lipid discs". M. Damian, J. Marie, J.P. Leyris, J.A. Fehrentz, P. Verdie, J. Martinez, J.L. Baneres, S. Mary. J. Biol. Chem. 287, 3630-3641 (2012).
• "Chemoselective cross-linking of alginate with thiol-terminated peptides for tissue engineering applications". S. Bubenikova, I.C. Stancu, L. Kalinovska, E. Schacht, E. Lippens, H. Declercq, M. Cornelissen, M. Santin, M. Amblard, J. Martinez. Carbohydr. Polym. 88, 1239-1250 (2012).
• "New 1,3-amino alcohols derived from enantiopure bridgehead beta-aminobicyclo[2.2.2]oct-5-ene-2-carboxylic acids". C. Andre, M. Calmes, F. Escale, M. Amblard, J. Martinez, O. SONGIS. Amino Acids 43, 415-421 (2012).
• "(S)-ABOC: A Rigid Bicyclic beta-Amino Acid as Turn Inducer". C. Andre, B. Legrand, C. Deng, C. Didierjean, G. Pickaert, J. Martinez, M.C. Averlant-Petit, M. Amblard, M. Calmes. Org. Lett. 14, 960-963 (2012).
• "Robust Helix Formation in a New Family of Oligoureas Based on a Constrained Bicyclic Building Block". B. Legrand, C. Andre, E. Wenger, C. Didierjean, M.C. Averlant-Petit, J. Martinez, M. Calmes, M. Amblard. Angew. Chem. Int. Ed. 51, 11267-11270 (2012).
• "Chemical Optimization of New Ligands of the Low-Density Lipoprotein Receptor as Potential Vectors for Central Nervous System Targeting". J.D. Malcor, N. Payrot, M. David, A. Faucon, K. Abouzid, G. Jacquot, N. Floquet, F. Debarbieux, G. Rougon, J. Martinez, M. Khrestchatisky, P. Vlieghe, V. Lisowski. J. Med. Chem. 55, 2227-2241 (2012).
• "Attenuation of cocaine-induced locomotor sensitization in rats sustaining genetic or pharmacologic antagonism of ghrelin receptors". P.S. Clifford, J. Rodriguez, D. Schul, S. Hughes, T. Kniffin, N. Hart, S. Eitan, L. Brunel, J.A. Fehrentz, J. Martinez, P.J. Wellman. Addict. Biol. 17, 956-963 (2012).
• "Tumor suppression by small molecule inhibitors of translation initiation". L.M. Chen, B.H. Aktas, Y.B. Wang, X.Y. He, R. Sahoo, N.C. Zhang, S. Denoyelle, E. Kabha, H.W. Yang, R.Y. Freedman, J.G. Supko, M. Chorev, G. Wagner, J.A. Halperin. Oncotarget 3, 869-U863 (2012).
• "An innovative strategy for sulfopeptides analysis using MALDI-TOF MS reflectron positive ion mode". S. Cantel, L. Brunel, K. Ohara, C. Enjalbal, J. Martinez, J.J. Vasseur, M. Smietana. Proteomics 12, 2247-2257 (2012).
• "Activation of alpha-secretase by curcumin-aminoacid conjugates". R.B. Narasingapa, M.R. Jargaval, S. Pullabhatla, H.H. Htoo, J.K.S. Rao, J.F. Hernandez, P. Govitrapong, B. Vincent. Biochem. Biophys. Res. Commun. 424, 691-696 (2012).
• "A New Highly Versatile Handle for Chemistry on a Solid Support: The Pipecolic Linker". N. Masurier, P. Zajdel, P. Verdie, M. Pawlowski, M. Amblard, J. Martinez, G. Subra. Chemistry-a European Journal 18, 11536-11540 (2012).