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Serge Bouaziz

Faculté de Pharmacie

Structural and functional studies of new therapeutic targets by NMR


Website: https://www.citcom.cnrs.fr
ORCID: 0000-0001-7792-8307

Structural and functional studies of new therapeutic targets by NMR
My research activity concerns the structural and functional study of new therapeutic targets. My objective is the structural characterization of these targets and their complexes by NMR in order to elucidate their mechanism of recognition and action, to translate these interactions into functional terms and to use these molecules as potential targets for the rational development of new therapeutic ligands. My research projects concern:
(A) HIV-1 proteins as targets (1) mechanism of action of HIV-1 maturation inhibitors, (2) interactions of the HIV-1 Vpr protein with the cellular restriction factor UNG2, with p6 protein and study of its chaperone effect on nucleic acids. (3) Structural studies of complexes between NCp7 and nucleic acids combining NMR and molecular dynamics and between NCp7 and p6, a potential regulator of RNA recognition by NCp7.
(B) Structural studies of the agnoprotein of the human polyomavirus, inhibition of the formation of dimers by mimetic peptides.
(C) Study of the polymerase complex of SARS-CoV-2 aimed at identifying ligands disrupting polymerase complex, activity and viral replication.
(D) Projects in collaboration with chemists: targeting of the VEGF-VEGFR1d2 protein interface, characterization of macrocyclic peptides stabilizing protein α-turns, DNA compaction in thiourea lipids, synthesis and structural studies of a new class of cyclin-dependent kinase inhibitors.

Top 5 publications

1- Chen X, Coric P, Bouaziz S. 1H, 13C and 15N backbone resonance assignment of HIV-1 Gag (276-432) encompassing the C-terminal domain of the capsid protein, the spacer peptide 1 and the nucleocapsid protein. Biomol NMR Assign. 2021 Oct;15(2):267-271. doi: 10.1007/s12104-021-10016-9. Epub 2021 Mar 22. PMID: 33754285.

2- Chen X, Coric P, Larue V, Turcaud S, Wang X, Nonin-Lecomte S, Bouaziz S. The HIV-1 maturation inhibitor, EP39, interferes with the dynamic helix-coil equilibrium of the CA-SP1 junction of Gag. Eur J Med Chem. 2020 Oct 15;204:112634. doi:10.1016/j.ejmech.2020.112634. Epub 2020 Jul 18. PMID: 32717487.

3- Wang X, Chen X, Nonin-Lecomte S, Bouaziz S. Acetonitrile allows indirect replacement of nondeuterated lipid detergents by deuterated lipid detergents for the nuclear magnetic resonance study of detergent-soluble proteins. Protein Sci. 2021 Nov;30(11):2324-2332. doi:10.1002/pro.4174. Epub 2021 Sep 9. PMID: 34462977; PMCID: PMC8521311.

4- Kara H, Chazal N, Bouaziz S. Is Uracil-DNA Glycosylase UNG2 a New Cellular Weapon Against HIV-1? Curr HIV Res. 2019;17(3):148-160. doi: 10.2174/1570162X17666190821154331. PMID: 31433761.

5- Coric P, Saribas AS, Abou-Gharbia M, Childers W, Condra JH, White MK, Safak M, Bouaziz S. Nuclear Magnetic Resonance Structure of the Human Polyoma JC Virus Agnoprotein. J Cell Biochem. 2017 Oct;118(10):3268-3280. doi: 10.1002/jcb.25977. Epub 2017 May 3. PMID: 28295503; PMCID: PMC5550335.

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