Chemistry and Modelling for Protein Recognition

Florence Mahuteau-Betzer

Florence Mahuteau-Betzer Team Leader Tel:

Our scientific goal is to provide, via organic chemistry and synthesis, small molecules as druggable candidates and chemical tools for a better understanding of biological processes in the field of cancer. The discovery of new molecules interacting with living organisms benefits from the team’s expertise in modeling and molecular dynamics.

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In parallel with these drug discovery projects, we are continuing to develop and optimize methods in organic chemistry in order to introduce molecular diversity and open new chemical space and on normal modes in order to implement…

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Thanks to the drug discovery expertise acquired through the collaboration with the biotech Abivax and through the development of ATP competitive kinase inhibitors, the team is developing medicinal chemistry on innovative projects in oncology in collaboration with biologists from Institut Curie. Our research focusses on non-ATP competitive inhibitors of kinase of the TAM family and on a receptor coupled to protein G identified as a potential target of melanoma. For these goals, the screening of the Curie-CNRS chemistry library is an asset to identify hits that require further hit-to-lead optimization.

The questions of subcellular detection, localization and quantification in cellular medium of small molecules are crucial in their development as chemical tools or as drugs. Therefore, we also pursue our efforts on development of new fluorophores for cellular subcompartments labelling as well as biosensors for protein labeling.

doublet_MT_modes_7_to_10 Internal motions of a microtubule doublet.
Flagellar microtubule doublet (MTD) assembly in vitro reveals a regulatory role of tubulin C-terminal tails. In support of the in vitroexperiments, we performed molecular simulations that showed that all MTD tails are not equivalent in this regulation (Science 363, 285-288 (2019)). In the movie presented here, we display four essential motions of MTD in the absence of the tubulin tails. These motions correspond to the four lowest-frequency normal modes.

 

Key publications

Year of publication 2019

Mouawad L., Beswick V., Jamin N., Montigny C., Quiniou E., Barbot T. (2019 Dec 18)

Deciphering the mechanism of inhibition of SERCA1a by sarcolipin using molecular simulations

bioRxiv : DOI : 10.1101/2019.12.17.879825
Abegão L.M.G., Fonseca R.D., Santos F.A., Rodrigues J.J., Kamada K., Mendonça C.R., Piguel S., De Boni L. (2019 Aug 23)

First molecular electronic hyperpolarizability of series of π-conjugated oxazole dyes in solution: an experimental and theoretical study

RSC Adv. : 9 : 26476-26482 : DOI : 10.1039/C9RA05246A
El Hassen Mokrani, Abderrahmane Bensegueni, Ludovic Chaput, Claire Beauvineau, Hanane Djeghim, Liliane Mouawad (2019 May 1)

Identification of New Potent Acetylcholinesterase Inhibitors Using Virtual Screening and In Vitro Approaches.

Molecular informatics : 38 : 1800118 : DOI : 10.1002/minf.201800118
Morgan Pellerano, Delphine Naud-Martin, Florence Mahuteau-Betzer, Marie Morille, May Catherine Morris (2019 Feb 15)

Fluorescent biosensor for detection of the R248Q aggregation-prone mutant of p53.

Chembiochem : a European journal of chemical biology : 20 : 605-613 : DOI : 10.1002/cbic.201800531
Pauline Gilson, Morgane Couvet, Laetitia Vanwonterghem, Maxime Henry, Julien Vollaire, Vladimir Baulin, Marco Werner, Anna Orlowska, Véronique Josserand, Florence Mahuteau-Betzer, Laurence Lafanechère, Jean-Luc Coll, Benoit Busser, Amandine Hurbin (2019 Feb 1)

The pyrrolopyrimidine colchicine-binding site agent PP-13 reduces the metastatic dissemination of invasive cancer cells in vitro and in vivo.

Biochemical pharmacology : 160 : 1-13 : DOI : S0006-2952(18)30503-3
Delphine Naud-Martin, Corinne Landras-Guetta, Daniela Verga, Deepanjan Ghosh, Sylvain Achelle, Florence Mahuteau-Betzer, Sophie Bombard, Marie-Paule Teulade-Fichou (2019 Jan 26)

Selectivity of Terpyridine Platinum Anticancer Drugs for G-quadruplex DNA.

Molecules (Basel, Switzerland) : 24 : 404 : DOI : 10.3390/molecules24030404
All publications