Discovery of peptidomimetic inhibitors of CREB/CBP by targeting hydrophobic grooves on the surface of the CBP KIX domain.

ABSTRACT: Cyclic AMP-response element binding protein (CREB), a downstream transcription factor of multiple signaling pathways, is overexpressed in many different types of cancers. Thus, targeting CREB has great potential for the development of antitumor agents. Peptidic foldamers have emerged as a powerful tool to disrupt disease-related protein-protein interactions (PPIs) with chemodiversity and high stability towards enzymatic degradation. Herein, we harnessed several hydrophobic groups of helical sulfonyl-γ-AApeptide foldamer targeting the hydrophobic grooves on the surface of the KIX domain of CREB binding protein (CBP), to disrupt CREB/CBP PPI. We showed that several stapled sulfonyl-γ-AApeptides could suppress CREB-mediated gene transcription and exhibit effective antiproliferat

SUBMITTER: Huang B 

PROVIDER: S-EPMC12750372 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature