Title :

Toward the Design of Ligands Selective for the C-Terminal Domain of TEADs.

Author(s) :

Liberelle, Maxime [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Toulotte, Florine [Auteur]
Lille Neurosciences & Cognition - U 1172 [LilNCog]
Renault, Nicolas [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Gelin, Muriel [Auteur]
Centre de Biologie Structurale [Montpellier] [CBS]
Allemand, Frédéric [Auteur]
Centre de Biologie Structurale [Montpellier] [CBS]
Melnyk, Patricia [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172
Guichou, Jean-François [Auteur]
Centre de Biologie Structurale [Montpellier] [CBS]
Cotelle, Philippe [Auteur]
Lille Neurosciences & Cognition (LilNCog) - U 1172

Journal title :

Journal of Medicinal Chemistry

Abbreviated title :

J Med Chem

Volume number :

65

Pages :

5926–5940

Publication date :

2022-04-17

ISSN :

1520-4804

English keyword(s) :

Interfaces
Ligands
Monomers
Peptides and proteins
Targeting

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

The Hippo signaling pathway plays a fundamental role in the control of organ growth, cell proliferation, and stem cell characters. TEADs are the main transcriptional output regulators of the Hippo signaling pathway and ...
Show more >The Hippo signaling pathway plays a fundamental role in the control of organ growth, cell proliferation, and stem cell characters. TEADs are the main transcriptional output regulators of the Hippo signaling pathway and bind to YAP and TAZ co-activators. TEAD1–4 are expressed differently, depending on the tissue and developmental level, and can be overexpressed in certain pathologies. TEAD ligands mainly target the internal pocket of the C-terminal domain of TEAD, and the first ligands selective for TEAD1 and TEAD3 have been recently reported. In this paper, we focus on the topographic homology of the TEAD C-terminal domain both externally and in the internal pocket to highlight the possibility of rationally designing ligands selective for one of the TEAD family members. We identified a novel TEAD2-specific pocket and reported its first ligand. Finally, AlphaFold2 models of full-length TEADs suggest TEAD autoregulation and emphasize the importance of the interface 2.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
• Lille Neurosciences & Cognition (LilNCog) - U 1172

Submission date :

2024-01-12T01:47:40Z
2024-02-28T08:41:32Z