Structure-based design of potent linear peptide inhibitors of the YAP-TEAD protein-protein interaction derived from the YAP omega-loop sequence.
Adaptor Proteins, Signal Transducing
/ antagonists & inhibitors
Dose-Response Relationship, Drug
Drug Design
Humans
Molecular Structure
Peptides
/ chemical synthesis
Protein Binding
/ drug effects
Small Molecule Libraries
/ chemical synthesis
Structure-Activity Relationship
Transcription Factors
/ antagonists & inhibitors
YAP-Signaling Proteins
Anticancer drug target
Protein-protein interaction (PPI) inhibitors
Structure-based design
Journal
Bioorganic & medicinal chemistry letters
ISSN: 1464-3405
Titre abrégé: Bioorg Med Chem Lett
Pays: England
ID NLM: 9107377
Informations de publication
Date de publication:
15 08 2019
15 08 2019
Historique:
received:
15
04
2019
revised:
13
06
2019
accepted:
17
06
2019
pubmed:
27
6
2019
medline:
23
9
2020
entrez:
26
6
2019
Statut:
ppublish
Résumé
The YAP-TEAD protein-protein interaction is a potential therapeutic target to treat cancers in which the Hippo signaling pathway is deregulated. However, the extremely large surface of interaction between the two proteins presents a formidable challenge for a small molecule interaction disrupter approach. We have accomplished progress towards showing the feasibility of this approach by the identification of a 15-mer peptide able to potently (nanomolar range) disrupt the YAP-TEAD interaction by targeting only one of the two important sites of interaction. This peptide, incorporating non-natural amino acids selected by structure-based design, is derived from the Ω-loop sequence 85-99 of YAP.
Identifiants
pubmed: 31235263
pii: S0960-894X(19)30402-0
doi: 10.1016/j.bmcl.2019.06.022
pii:
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Peptides
0
Small Molecule Libraries
0
Transcription Factors
0
YAP-Signaling Proteins
0
YAP1 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2316-2319Informations de copyright
Copyright © 2019 Elsevier Ltd. All rights reserved.