Author: mbelev

Ludovic Maillard

Ludovic Maillard

Ludovic Maillard
Assistant Professor, Faculty of Pharmacy, Montpellier University

Ludovic Maillard is Pharmacyst (Paris XI, 2002) and Chemical Engineer (ENSCP, Paris VI, 2002). After a Master Degree in organic chemistry (Paris VI, 2002), he did a PhD in bioorganic chemistry at the ICSN, in the group of Dr. B. Badet. Thereafter he joined the group of Prof. J. Robinson (OCI, Zurich, Switzerland) for a one-year post-doctoral fellow. He is actually Assistant Professor in medicinal chemistry.

One of his major research interests is to develop and characterized conformationaly predictable molecular architectures named foldamers, which are constructed from heterocyclic γ-amino acids. In such a context, he has reported a short chemical route to access orthogonally protected thiazole-based γ-amino acids, which were used as building blocks for designing helical γ-peptide foldmers and antimicrobial peptides. These platforms are highly versatile and efforts are made to expand their applications toward cellular targeting and organo-catalysis.

Contact:

ludovic.maillard@umontpellier.Fr

(+33) 04 11 75 96 04

5 major publications : 

C. Bonnel, B. Legrand, M. Simon, J. Martinez, J.L. Bantignies, Y.K. Kang, E. Wenger, Francois Hoh, N. Masurier, L. T. Maillard* (2017)C9/12 Ribbon-Like Structures in Hybrid Peptides Alternating α- and Thiazole-Based γ-Amino Acids, Chem. Eur. J.17584-17591

Bonnel C., Legrand B., Bantignies J.-L., Petitjean H., Martinez J., Masurier N. and Maillard L. T.* (2016) FT-IR and NMR structural markers for thiazole-based γ-peptide foldamers Org. Biomol. Chem. 8664-8669.

Mathieu L., Bonnel C., Masurier N., Maillard L. T.*, Martinez J. and Lisowski V. (2015) Cross-Claisen Condensation of N-Fmoc-Amino Acids – A Short Route to Heterocyclic γ-Amino Acids Eur. J. Org. Chem. 2262–2270.

Legrand B., Mathieu L., Lebrun A., Andriamanarivo S., Lisowski V., Masurier N., Zirah S., Kang Y. K., Martinez J., Maillard L.T.*, (2014) Thiazole-Based γ-Building Blocks as Reverse-Turn Mimetic to Design a Gramicidin S Analogue: Conformational and Biological Evaluation Chem. Eur. J. 6713-6720.

Mathieu L., Legrand B., Deng C., Vezenkov L., Wenger E., Didierjean C., Amblard M., Averlant-Petit MC., Masurier N., Lisowski V., Martinez J. and Maillard L.T.* (2013) Helical Oligomers of Thiazole-Based γ-Amino Acids: Synthesis and Structural Studies. Angew. Chem. Int. Ed. 52, 6006-6010.

Jean-François Hernandez

JEAN-FRANÇOIS HERNANDEZ

Jean-françois hernandez
Research Director (CNRS)

Jean-François Hernandez performed his PhD in the laboratory of Prof. Bernard P. Roques (Paris V University, 1987) under the supervision of Prof. Marie-Claude Fournié-Zaluski, where he developed pseudo-dipeptidic inhibitors of enkephalin-degrading enzymes as potential analgesics. Then, he went to the Salk Institute in San Diego as a post-doctoral fellow (1988-1990) under the supervision of Prof. Jean E. Rivier, where he learned solid phase peptide synthesis (Boc and Fmoc chemistries, GRF agonists, CRF antagonists, conotoxins, long peptides).

After moving back to France, he obtained a two-years temporary assistant professor position (ATER, 1990-1992) in the laboratory of Prof. Joëlle Paris at the faculty of Pharmacy of Lyon, where he developed SPPS methodology and worked on a project related to immunology. He obtained a permanent research position at the CNRS in 1992 and joined the team of Gérard Arlaud at Institut de Biologie Structurale in Grenoble, where he mainly performed the solid phase synthesis of peptides for fundamental and/or structural studies. He also contributed to the characterization of natural peptidase inhibitors (squash trypsin inhibitors like MCoTI) and of microbial peptidases.

In 2001, he moved to the laboratory of Prof. Jean Martinez (Laboratoire des Amino acides, Peptides et Protéines) in Montpellier, where he started to supervise  a small group devoted to the development of enzyme inhibitors (pseudo-peptides, heterocycles) with therapeutical interest. Among targets that were or are currently explored: parasitic peptidases (Plasmodium, Leishmania), beta-lactamases, NO Synthases, Cathepsin D, secretases. A second important part of its activity is the development of solid phase synthetic strategies in the peptide/pseudopeptide field. In particular, he developed several strategies for the preparation of arginine- and arginine-like-containing compounds.

Contact:

jean-francois.hernandez(at)umontpellier.fr

+33 (0)4 11 75 96 03

5 major publications :

Vezenkov L. L., Sanchez C.A., Bellet V., Martin V., Maynadier M., Lisowski V., Martinez J.,Garcia M., Amblard M. & Hernandez J.-F. (2016) Structure-activity relationships of JMV4463, a vectorized Cathepsin D inhibitor with antiproliferative properties: the unique role of the AMPA-based vector. ChemMedChem 11, 302-308.

Touati-Jallabe Y., Bojnik E., Legrand B., Mauchauffée E., Chung N. N., Schiller P. W., Benyhe S., Averlant-Petit M.-C., Martinez J. & J. F. Hernandez (2013) Cyclic enkephalins with a diversely substituted guanidine bridge or a thiourea bridge: synthesis, biological and structural evaluations,  J. Med. Chem. 56, 5964-5973.

Peuchmaur M., Lacour M.-A., Sévalle J., Lisowski V., Touati-Jallabe Y., Rodier F., Martinez J., Checler F. & J. F. Hernandez (2013) Further characterization of a putative serine protease contributing to the g-secretase cleavage of b-amyloid precursor protein, Bioorg. Med. Chem. 21, 1018-1029.

Nauton L., Kahn R., Garau G., Hernandez J.-F. & Dideberg O. (2008) Structural insights into the design of inhibitors for the L1 metallo-b-lactamase from Stenotrophomonas maltophilia, J. Mol. Biol. 375, 257-269.

Hamzé A., Martinez J. & Hernandez J.-F. (2004) Solid-phase synthesis of arginine-containing peptides and fluorogenic substrates using a side-chain anchoring approach. J. Org. Chem. 69, 8394-8402.

Jean-Alain Fehrentz

Jean-Alain Fehrentz
Research Director (CNRS)

Jean-Alain Fehrentz was born in Nancy, France, in 1955. He received his Ph.D. degree in Chemistry from the University of Nancy in 1983 and joined the Centre CNRS-INSERM de Pharmacologie Endocrinologie of Montpellier in the research group of Professor B. Castro. From 1989 to 1992 he was appointed as researcher at Sanofi Research in Montpellier. Then he moved to the Faculty of Pharmacy of Montpellier, working under the direction of Professor J. Martinez.

His research interests focus onpeptide aldehydes, enzyme inhibitors, peptidomimetics, and heterocycle based receptor ligands. He published more than 150 scientific papers.

Contact:

jean-alain.fehrentz(at)univ-montp1.fr

+33 411 75 96 06

5 major publications

L.S. Chatalic, M. Konijnenberg, J. Nonnekens, E. De Blois, S. Hoeben, C. De Ridder, L. Brunel, J. Martinez,  J.-A. Fehrentz, D. C. Van Gent, B. A. Nock, T. Maina, W. M. Van Weerden, M. De Jong; In Vivo Stabilization of GRPR-peptide enhances PET Imaging and Radionuclide Therapy of Prostate Cancer in Preclinical Studies. Theranostics 2016 6 (1), 104-117

G. P. Denis, A. Joly-Amado, E. Webber , F. Langlet,, M. Schaeffer, S. Padilla, C. Cansell, B. Dehouck, J. Castel, A.-S. Delbès, S.Martinez, A. Lacombe, C. Rouch, N. Kassis, J.-A. Fehrentz, J. Martinez, P. Verdié, T. S. Hnasko, R. D. Palmiter, M. Krashes, A. D. Güler, C. Magnan, S. Luquet; Palatability can drive feeding independent of AgRP neurons Cell Metab 2015 22, 4, 646-657

Damian, S. Mary, M. Maingot, C. M’Kadmi, D. Gagne, J-P. Leyris, S. Denoyelle, G. Gaibelet, L. Gavara, M. Garcia De Souza Costa, D. Perahia, E. Trinquet, B. Mouillac, S. Galandrin, C. Gales, J-A. Fehrentz, N. Floquet, J. Martinez, J. Marie, J-L. Baneres;  Ghrelin receptor conformational dynamics regulate the transition from a preassembled to an active receptor:Gq complex. PNAS 2015 112 (5) 1601-1606 (2015)

Schaeffer, F. Langlet, C. Lafont, F. Molino, D. J. Hodson, T. Roux, L. Lamarque, P. Verdié, E. Bourrier, B. Dehouck, J.-L. Baneres, J. Martinez, P.-F. Méry, J. Marie, E. Trinquet, J.-A. Fehrentz, V. Prévot, P. Mollard; Rapid sensing of circulating ghrelin by hypothalamic appetite-modifying neurons. PNAS 2013 110(4) 1512-1517

J. -A. Fehrentz, B. Castro; An efficient synthesis of optically active -(t-butoxycarbonylamino)-aldehydes from -amino-acids. Synthesis 1983, vol 8, 676-679

Baptiste Legrand

Baptiste legrand
Research Engineer, University of Montpellier (UM)

Baptiste is a Research Engineer at the Institute of Biomolecules Max Mousseron (IBMM), University of Montpellier. He received his PhD in biology and life sciences from the University of Rennes 1 in 2009. Then, he moved for a two years post-doctoral fellowship at the Laboratory of Macromolecular Chemistry and Physics (LCPM, Nancy) working on the characterization of foldamers structures combining various techniques (NMR, CD and FTIR spectroscopies, and Molecular Dynamics) and then he joined the IBMM in 2012. His research is mainly devoted on the rational design of peptidomimetics and organized molecular architectures to modulate biological processes focusing on the structural aspects. He is in charge of the conformational studies of various chemical tools developed at the IBMM but also collaborates with other groups.

Contact:
baptiste.legrand@umontpellier.fr
+33 411 75 96 06

5 major publications :

Legrand B, André C, Moulat L, Didierjean C, Hermet P, Bantignies JL, Martinez J, Amblard M, Calmès M. 12/14/14-Helix Formation in 2:1 α/β-Hybrid Peptides Containing Bicyclo[2.2.2]octane Ring Constraints. Chemistry. 2016. 16;22(34):11986-90.

Martin V, Legrand B, Vezenkov LL, Subra G, Calmès M, Bantignies J.L, Martinez J,  Amblard M. Turning Peptide Sequences into Ribbon Foldamers by a Straightforward Multicyclization Reaction. Angew. Chem. Int. Ed. 2015. 16;54(47):13966-70.

Legrand B, André C, Moulat L, Wenger E, Didierjean C, Aubert E, Averlant-Petit MC, Martinez J, Calmes M, Amblard M. Unprecedented chain-length-dependent conformational conversion between 11/9 and 18/16 helix in α/β-hybrid peptides. Angew Chem Int Ed. 2014. 53(48):13131-5.

Mathieu L, Legrand B, Deng C, Vezenkov L, Wenger E, Didierjean C, Amblard M, Averlant-Petit MC, Masurier N, Lisowski V, Martinez J, Maillard LT. Helical oligomers of thiazole-based γ-amino acids: synthesis and structural studies. Angew Chem Int Ed. 2013. 3;52(23):6006-10.

Legrand B, André C, Wenger E, Didierjean C, Averlant-Petit MC, Martinez J, Calmes M, Amblard M. Robust helix formation in a new family of oligoureas based on a constrained bicyclic building block. Angew Chem Int Ed. 2012. 51(45):11267-70.

Lubomir Vezenkov

Lubomir Vezenkov portrait

Lubomir Vezenkov

ASSISTANT Professor, National Graduate School of Chemistry of Montpellier

Lubomir Vezenkov performed a co-tutoring PhD between the universities of Montpellier and Naples, under the supervision of Prof. Jean Martinez and Prof. Ettore Benedetti, which he graduated from in 2011. Afterwards he did a two-years-long post-doctoral internship in the prof. Robert Young group in Simon Fraser University, Vancouver, working on the development of selective inhibitors of the autophagy. In 2013 he moved back to Montpellier to perform a post-doctoral study under the supervision of Dr. Muriel Amblard and in 2016 he received an assistant professor position at The National Graduate School of Chemistry of Montpellier (ENSCM).

His research currently is focalized on the development of organized non-natural oligomers, termed foldamers, and their applications in the biomedical field. He is especially interested in the conception of potent and bioavailable vectors for intracellular penetration. He has recently ventured in the exciting field of the peptide functionalized polymers and their structural and functional characterization

lubomir.vezenkov@enscm.fr
+33 411 75 96 27

5 major publications :

1) Martin, B. Legrand, L. L. Vezenkov, G. Subra, M. Calmès, J. Bantignies, J. Martinez, M. Amblard; Turning Peptide Sequences into Ribbon Foldamers by a Straightforward Multicyclization Reaction. Angew. Chem. Int. Ed. 2015 Nov 16;54(47):13966-70

2) L. Vezenkov, N. Honson, N. Kumar, D. Bosc, S. Kovacic, T. Nguyen, T. Pfeifer, R. Young; Development of fluorescent peptide substrates and assays for the key autophagy-initiating cysteine protease enzyme, ATG4B. Bioorg Med Chem. 2015 Jul 1;23(13):3237-47

3)  L. L. Vezenkov, Maynadier M, Amblard M, Martin V, Gandreuil C, Vaillant O, Gary-Bobo M, Basile I, Hernandez JF, Garcia M, Martinez J; Dipeptide mimic oligomer transporter mediates intracellular delivery of Cathepsin D inhibitors: a potential target for cancer therapy. Journal of controlled release. 2013, Oct 28;171(2):251-7.

4) L. Vezenkov, M. Maynadier, J. F. Hernandez, M. Averlant-Petit, O. Fabre, E. , M. Garcia, J. Martinez and M. Amblard; Noncationic Dipeptide Mimic Oligomers As Cell Penetrating Nonpeptides(CPNP). Bioconjugate Chem. 2010, 21(10), 1850–1854.

5) D. Paramelle, G. Subra, L. L. Vezenkov, M. Maynadier, C. Andre, C. Enjalbal, M. Calmes, M. Garcia, J. Martinez, and M. Amblard; A Straightforward Approach for Cellular-Uptake Quantification. Angew. Chem. Int. Ed. 2010, 49(44), 8240-8243.

 

Severine Denoyelle

Séverine Denoyelle

SEvErine Denoyelle
ASSISTANT Professor, Faculty of Pharmacy of Montpellier

After defending her Ph.D. in the field of bioorganic chemistry in 2005, Severine joined the Faculty of Pharmacy of Montpellier as a postdoctoral fellow. As part of the European project “Antimal”, her research work consisted in the development of new oral drugs for the treatment of Malaria. In 2007, Séverine started a two-year postdoctoral position at Harvard Medical School, Boston, MA, where she focused on the design and the synthesis of small molecules, namely diarylureas and oxindoles, for cancer therapy.

In 2009, she became assistant professor in medicinal chemistry at the Faculty of Pharmacy of Montpellier where she joined the Institute of Biomolecules Max Mousseron (IBMM). Her main research project focuses on the development of ligands targeting the Ghrelin receptor (GHS-R1a), a GPCR that mediates growth hormone secretion, food intake, and reward-seeking behaviors. Because of its possible implication in several physiological disorders such as obesity and drugs/alcohol addictions, GHS-R1a represents a major target for the development of therapeutic small molecules.

More recently, Séverine has also been interested in the development of new methodologies to access heterocyclic scaffolds such as [1,2,4]triazoles, diazepinones and triazole-ketopiperazines in order to find new potential lead compounds for therapeutic applications.

Contact:
severine.denoyelle@umontpellier.fr
+33 (0)4 11 75 96 35

5  major publications :

M. Maingot, A.-L. Blayo, S. Denoyelle, C. M’Kadmi, M. Damian, S. Mary, D. Gagne, P. Sanchez, B. Aicher, P. Schmidt, G. Müller, M. Teifel, E. Günther, J. Marie, J.-L. Banères, J. Martinez, J.-A. Fehrentz. New ligands of the ghrelin receptor based on the 1,2,4-triazole scaffold by introduction of a second chiral center. Bioorg. Med. Chem. Lett. 2016, 26, 2408-2412.

S. Denoyelle, G. Tambutet, N. Masurier, L. T. Maillard, J. Martinez, V. Lisowski. Synthesis of Thieno[3,2-e][1,4]diazepin-2-ones: Application of an Uncatalysed Pictet–Spengler Reaction. Eur. J. Org. Chem. 2015, 32, 7146-7153.

S. Denoyelle, T. Chen, H. Yang, L. Chen, Y. Zhang, J. A. Halperin, B. H. Aktas, M. Chorev. Synthesis and SAR study of novel 3,3-diphenyl-1,3-dihydroindol-2-one derivatives as potent eIF2·GTP·Met-tRNAiMet ternary complex inhibitors, Eur. J. Med. Chem. 2013, 69, 537-553.

T. Chen, D. Ozel, Y. Qiao, F. Harbinski, L. Chen, S. Denoyelle, X. He, N. Zvereva, J. G. Supko, M. Chorev, J. A. Halperin, B. H. Aktas. Chemical Genetics Identify eiF2α Kinase Hemeregulated Inhibitor as an Anticancer Target. Nat. Chem. Biol. 2011, 7(9), 610-616.

S. Ortial, S. Denoyelle, S. Wein, O. Berger, T. Durand, R. Escale, A. Pellet, H. Vial, Y. Vo-Hoang. Synthesis and Evaluation of Hybrid Bis-cationic Salts as Antimalarial Drugs. ChemMedChem 2010, 5, 52-55.

Gilles Subra

Gilles Subra

Gilles Subra
Professor, Faculty of Pharmacy of Montpellier

Gilles leads his researches in the Institute of Biomolécules Max Mousseron (IBMM) in the field of peptide science. His main research topics are at the interface of chemistry and biology and notably concern methodologies for solid phase and combinatorial chemistry, design of chemical tools to enhance detection and quantification by mass spectrometry in biological media. More recently, he is interested in the design of peptide-based materials and polymers. The main applications concern the conception of multi-ligand nanoparticles for cancer targeting, the functionalisation of silicone medical devices and dressings. His most recent research is related to the design of biomimetic peptide based hydrogel used for 3D biofabrication and cell-based therapies.

Gilles Subra founded the solid phase and automated synthesis platform (SynBio3) of the IBMM whose mission is to develop solid supported reagents, linkers and methodologies for the synthesis of biomolecules.

Contact:
gilles.subra@umontpellier.fr
+33 411 75 96 06

5 major publications :

Ciccione, J., Jia, T., Coll, J.-L., Parra, K., Amblard, M., Jebors, S., Martinez, J., Mehdi, A., and Subra, G. (2016). Unambiguous and Controlled One-Pot Synthesis of Multifunctional Silica Nanoparticles. Chem. Mater. 28, 885–889.

Echalier, C., Pinese, C., Garric, X., Van Den Berghe, H., Jumas Bilak, E., Martinez, J., Mehdi, A., and Subra, G. (2016). Easy Synthesis of Tunable Hybrid Bioactive Hydrogels. Chem. Mater. 28, 1261–1265.

Jebors, S., Ciccione, J., Al-Halifa, S., Nottelet, B., Enjalbal, C., M’Kadmi, C., Amblard, M., Mehdi, A., Martinez, J., and Subra, G. (2015). A New Way to Silicone-Based Peptide Polymers. Angew. Chem. Int. Ed. 54, 3778–3782.

Paramelle, D., Subra, G., Vezenkov, L.L., Maynadier, M., André, C., Enjalbal, C., Calmès, M., Garcia, M., Martinez, J., and Amblard, M. (2010). A Straightforward Approach for Cellular-Uptake Quantification. Angewandte Chemie International Edition 49, 8240–8243.

Paramelle, D., Enjalbal, C., Amblard, M., Forest, E., Heymann, M., Cantel, S., Geourjon, C., Martinez, J., and Subra, G. (2011). Solid-Phase Cross-Linking (SPCL): A new tool for protein structure studies. PROTEOMICS 11, 1277–1286.