Structure-based design of potent linear peptide inhibitors of the YAP-TEAD protein-protein interaction derived from the YAP omega-loop sequence. Issue 16 (15th August 2019)

• Record Type: Journal Article
• Authors: Furet, Pascal; Salem, Bahaa; Mesrouze, Yannick; Schmelzle, Tobias; Lewis, Ian; Kallen, Joerg; Chène, Patrick
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 29:Issue 16(2019)
• Page Start: 2316
• Page End: 2319
• Publication Date: 2019-08-15
• Subjects: Protein-protein interaction (PPI) inhibitors -- Anticancer drug target -- Structure-based design; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2019.06.022
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: 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.