M Yves Jacquot » Equipe : Chimie médicinale et recherche translationnelle

M Yves Jacquot

Professeur Université Paris CitéCiTCoM
Tel :: Numéro

Informations

Après des études de pharmacie à l’Université de Franche-Comté et un DEA en chimie fine à la faculté des sciences de Nantes, je me suis orienté vers la chimie médicinale. Durant ma thèse de doctorat, j’ai travaillé sur la pharmacomodulation de dérivés benzopyraniques à activité œstrogénique et anti-œstrogénique (1998-2001, faculté de pharmacie, Besançon) et, pendant mon stage de post-doctorat (2001-2002, ICOA, Orléans), sur la synthèse de modulateurs pseudopeptidiques de VLA-4. Recruté en 2002 comme maître de conférences à l’université Pierre et Marie Curie (Sorbonne Université), j’ai intégré le CNRS et me suis orienté vers la synthèse peptidique, la modélisation moléculaire et les études biophysiques des interactions ligand – protéine et peptide – membrane. De 2009 à 2019, j’ai été rattaché à l’Ecole Normale Supérieure (site Ulm). Mes activités de recherche se sont focalisées sur la synthèse de modulateurs peptidiques des domaines SH3 de la protéine Grb2 ainsi que sur la synthèse de modulateurs des voies œstrogéniques. Parallèlement à mes travaux sur le cancer du sein, j’ai développé, en collaboration avec l’équipe du professeur E.E. Baulieu, des ligands de la protéine FKBP52, un partenaire des récepteurs des hormones stéroïdes possiblement impliqué dans la maladie d’Alzheimer.

En 2019, j’ai intégré le laboratoire CiTCoM (CNRS UMR 8038, INSERM U 1268), où je travaille sur la synthèse de molécules modulatrices de la protéine GPER (G protein-coupled estrogen receptor), un récepteur à sept domaines transmembranaires impliqué dans de nombreux processus physiopathologiques (cancer, nociception, immunité, métabolisme, cardio-protection, neuroprotection,…).

Membre de sociétés scientifiques : SAPhS (Swiss Academy of Pharmaceutical Sciences), SCT (Société de Chimie Thérapeutique), GP2A (Group for the Promotion of Pharmaceutical chemistry in Academia), SCG (Schweizerische Chemische Gesellschaft), EPS (European Peptide Society)

Activités éditoriales :

– Molecular and Structural Endocrinology – Frontiers in Endocrinology (Associate Editor)

– Cells (Topic Editor)

Recherche :

– Synthèse hétérocyclique et peptidique

– Chimie médicinale

– Etudes biophysiques d’interactions ligand – protéine et peptide – membrane

– Modulation des voies transcriptionnelles associées aux œstrogènes

– Cancer du sein

Enseignement :

– PASS, LAS : « Conception du médicament, identification d’une molécule à visée thérapeutique »

– DFGSP3 : Chimie thérapeutique

– DFASP1 : Chimie thérapeutique

– M1 : « Pharmacologie et pharmacochimie »

– M2 : « Récepteur pharmacologique et médicament »

« Chimie médicinale et pharmacologie moléculaire »

Publications

  1. Jouffre, B, Acramel, A, Jacquot, Y, Daulhac, L, Mallet, C(2023)GPER involvement in inflammatory pain. Steroids 200 :109311.
  2. Kampa, M et al.(2023)Promising Perspectives of the Antiproliferative GPER Inverse Agonist ERα17p in Breast Cancer. Cells 12 (4):.
  3. Jacquot, Y, de Cremoux, P, Harvey, BJ, Wehling, M(2023)The Rapid Responses to Steroid Hormones meetings: An important event for steroid science. Ann Endocrinol (Paris) 84 (2):235-237.
  4. Terrien, A et al.(2023)Inviting C5-Trifluoromethylated Pseudoprolines into Collagen Mimetic Peptides. Biomacromolecules 24 (4):1555-1562.
  5. Jouffre, B et al.(2023)Identification of a human estrogen receptor α tetrapeptidic fragment with dual antiproliferative and anti-nociceptive action. Sci Rep 13 (1):1326.
  6. Acramel, A, Jacquot, Y(2022)Deciphering of a Putative GPER Recognition Domain in ERα and ERα36. Front Endocrinol (Lausanne) 13 :943343.
  7. Jacquot, Y, Kampa, M, Lindsey, SH(2021)Editorial: GPER: Control and Functions. Front Endocrinol (Lausanne) 12 :794344.
  8. Jacquot, Y, Kampa, M, Lindsey, SH(2021)Editorial: GPER and Human Pathologies. Front Endocrinol (Lausanne) 12 :794332.
  9. Mallet, C et al.(2021)The Antitumor Peptide ERα17p Exerts Anti-Hyperalgesic and Anti-Inflammatory Actions Through GPER in Mice. Front Endocrinol (Lausanne) 12 :578250.
  10. de la Sierra-Gallay, IL et al.(2020)Bioinspired Hybrid Fluorescent Ligands for the FK1 Domain of FKBP52. J Med Chem 63 (18):10330-10338.
  11. Grande, F et al.(2020)Computational Approaches for the Discovery of GPER Targeting Compounds. Front Endocrinol (Lausanne) 11 :517.
  12. Trichet, M et al.(2020)Interaction of the Anti-Proliferative GPER Inverse Agonist ERα17p with the Breast Cancer Cell Plasma Membrane: From Biophysics to Biology. Cells 9 (2):.
  13. Yip, F et al.(2019)Improvement of the anti-proliferative activity of the peptide ERα17p in MCF-7 breast cancer cells using nanodiamonds. Ann Pharm Fr 77 (6):488-495.
  14. Lappano, R et al.(2019)The Peptide ERα17p Is a GPER Inverse Agonist that Exerts Antiproliferative Effects in Breast Cancer Cells. Cells 8 (6):.
  15. Lappano, R, Jacquot, Y, Maggiolini, M(2018)GPCR Modulation in Breast Cancer. Int J Mol Sci 19 (12):.
  16. Despres, C et al.(2017)Identification of the Tau phosphorylation pattern that drives its aggregation. Proc Natl Acad Sci U S A 114 (34):9080-9085.
  17. Jacquot, Y et al.(2017)ERE-dependent transcription and cell proliferation: Independency of these two processes mediated by the introduction of a sulfone function into the weak estrogen estrothiazine. Eur J Pharm Sci 109 :169-181.
  18. Byrne, C et al.(2016)A β-Turn Motif in the Steroid Hormone Receptor's Ligand-Binding Domains Interacts with the Peptidyl-prolyl Isomerase (PPIase) Catalytic Site of the Immunophilin FKBP52. Biochemistry 55 (38):5366-76.
  19. Leclercq, G et al.(2017)ERα dimerization: a key factor for the weak estrogenic activity of an ERα modulator unable to compete with estradiol in binding assays. J Recept Signal Transduct Res 37 (2):149-166.
  20. Kamah, A et al.(2016)Isomerization and Oligomerization of Truncated and Mutated Tau Forms by FKBP52 are Independent Processes. J Mol Biol 428 (6):1080-1090.
  21. Miclet, E, Bourgoin-Voillard, S, Byrne, C, Jacquot, Y(2016)Application of Circular Dichroism Spectroscopy to the Analysis of the Interaction Between the Estrogen Receptor Alpha and Coactivators: The Case of Calmodulin. Methods Mol Biol 1366 :241-259.
  22. Leiber, D et al.(2015)The sequence Pro295-Thr311 of the hinge region of oestrogen receptor α is involved in ERK1/2 activation via GPR30 in leiomyoma cells. Biochem J 472 (1):97-109.
  23. Gandhi, NS et al.(2015)A Phosphorylation-Induced Turn Defines the Alzheimer's Disease AT8 Antibody Epitope on the Tau Protein. Angew Chem Int Ed Engl 54 (23):6819-23.
  24. Ruggeri, FS et al.(2015)Concentration-dependent and surface-assisted self-assembly properties of a bioactive estrogen receptor α-derived peptide. J Pept Sci 21 (2):95-104.
  25. Byrne, C et al.(2013)Identification of polyproline II regions derived from the proline-rich nuclear receptor coactivators PNRC and PNRC2: new insights for ERα coactivator interactions. Chirality 25 (10):628-42.
  26. Frankiewicz, L et al.(2013)Stabilisation of a short α-helical VIP fragment by side chain to side chain cyclisation: a comparison of common cyclisation motifs by circular dichroism. J Pept Sci 19 (7):423-32.
  27. Notas, G et al.(2013)Whole transcriptome analysis of the ERα synthetic fragment P295-T311 (ERα17p) identifies specific ERα-isoform (ERα, ERα36)-dependent and -independent actions in breast cancer cells. Mol Oncol 7 (3):595-610.
  28. Leclercq, G, Jacquot, Y(2014)Interactions of isoflavones and other plant derived estrogens with estrogen receptors for prevention and treatment of breast cancer-considerations concerning related efficacy and safety. J Steroid Biochem Mol Biol 139 :237-44.
  29. Bourgoin-Voillard, S et al.(2012)Electronic effects of 11β substituted 17β-estradiol derivatives and instrumental effects on the relative gas phase acidity. J Am Soc Mass Spectrom 23 (12):2167-77.
  30. Byrne, C et al.(2012)ERα17p, a peptide reproducing the hinge region of the estrogen receptor α associates to biological membranes: A biophysical approach. Steroids 77 (10):979-87.
  31. Carlier, L et al.(2012)Biophysical studies of the interaction between calmodulin and the R²⁸⁷-T³¹¹ region of human estrogen receptor α reveals an atypical binding process. Biochem Biophys Res Commun 419 (2):356-61.
  32. Kampa, M et al.(2011)ERα17p, an ERα P295 -T311 fragment, modifies the migration of breast cancer cells, through actin cytoskeleton rearrangements. J Cell Biochem 112 (12):3786-96.
  33. This, P, de Cremoux, P, Leclercq, G, Jacquot, Y(2011)A critical view of the effects of phytoestrogens on hot flashes and breast cancer risk. Maturitas 70 (3):222-6.
  34. Leclercq, G et al.(2011)Peptides targeting estrogen receptor alpha-potential applications for breast cancer treatment. Curr Pharm Des 17 (25):2632-53.
  35. Pelekanou, V et al.(2011)The estrogen receptor alpha-derived peptide ERα17p (P(295)-T(311)) exerts pro-apoptotic actions in breast cancer cells in vitro and in vivo, independently from their ERα status. Mol Oncol 5 (1):36-47.
  36. Leclercq, G, de Cremoux, P, This, P, Jacquot, Y(2011)Lack of sufficient information on the specificity and selectivity of commercial phytoestrogens preparations for therapeutic purposes. Maturitas 68 (1):56-64.
  37. de Cremoux, P, This, P, Leclercq, G, Jacquot, Y(2010)Controversies concerning the use of phytoestrogens in menopause management: bioavailability and metabolism. Maturitas 65 (4):334-9.
  38. Bourgoin-Voillard, S et al.(2010)Capacity of type I and II ligands to confer to estrogen receptor alpha an appropriate conformation for the recruitment of coactivators containing a LxxLL motif-Relationship with the regulation of receptor level and ERE-dependent transcription in MCF-7 cells. Biochem Pharmacol 79 (5):746-57.
  39. Sachon, E, Clodic, G, Blasco, T, Jacquot, Y, Bolbach, G(2009)In-source fragmentation of very labile peptides in matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Anal Chem 81 (21):8986-92.
  40. Bourgoin-Voillard, S et al.(2009)Stereochemical effects during [M-H]- dissociations of epimeric 11-OH-17beta-estradiols and distant electronic effects of substituents at C(11) position on gas phase acidity. J Am Soc Mass Spectrom 20 (12):2318-33.
  41. Kapitán, J et al.(2009)Identification of a human estrogen receptor alpha-derived antiestrogenic peptide that adopts a polyproline II conformation. J Pept Sci 15 (7):455-64.
  42. Gallo, D, Jacquot, Y, Laurent, G, Leclercq, G(2008)Calmodulin, a regulatory partner of the estrogen receptor alpha in breast cancer cells. Mol Cell Endocrinol 291 (1-2):20-6.
  43. Gallo, D et al.(2008)Regulatory function of the P295-T311 motif of the estrogen receptor alpha - does proteasomal degradation of the receptor induce emergence of peptides implicated in estrogenic responses?. Nucl Recept Signal 6 :e007.
  44. Gallo, D et al.(2008)Trophic effect in MCF-7 cells of ERalpha17p, a peptide corresponding to a platform regulatory motif of the estrogen receptor alpha--underlying mechanisms. J Steroid Biochem Mol Biol 109 (1-2):138-49.
  45. Gallo, D et al.(2007)Calmodulin-independent, agonistic properties of a peptide containing the calmodulin binding site of estrogen receptor alpha. Mol Cell Endocrinol 268 (1-2):37-49.
  46. Jacquot, Y et al.(2007)Synthesis, structure, and estrogenic activity of 4-amino-3-(2-methylbenzyl)coumarins on human breast carcinoma cells. Bioorg Med Chem 15 (6):2269-82.
  47. Jacquot, Y, Gallo, D, Leclercq, G(2007)Estrogen receptor alpha--identification by a modeling approach of a potential polyproline II recognizing domain within the AF-2 region of the receptor that would play a role of prime importance in its mechanism of action. J Steroid Biochem Mol Biol 104 (1-2):1-10.
  48. Jacquot, Y et al.(2007)High affinity Grb2-SH3 domain ligand incorporating Cbeta-substituted prolines in a Sos-derived decapeptide. Bioorg Med Chem 15 (3):1439-47.
  49. Seo, HS et al.(2006)Stimulatory effect of genistein and apigenin on the growth of breast cancer cells correlates with their ability to activate ER alpha. Breast Cancer Res Treat 99 (2):121-34.
  50. Jacquot, Y, Zoubir, B, Xicluna, A, Bidet, AC(2006)[Research of 99mTcO4- and 99mTcO2- in injectable solutions of 99mTc-HMDP by inverse phase HPTLC]. Ann Pharm Fr 64 (1):63-7.
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