Peptide Tethering: Pocket-Directed Fragment Screening for Peptidomimetic Inhibitor Discovery.

ABSTRACT: Constrained peptides have proven to be a rich source of ligands for protein surfaces, but are often limited in their binding potency. Deployment of nonnatural side chains that access unoccupied crevices on the receptor surface offers a potential avenue to enhance binding affinity. We recently described a computational approach to create topographic maps of protein surfaces to guide the design of nonnatural side chains [J. Am. Chem. Soc. 2017, 139, 15560]. The computational method, AlphaSpace, was used to predict peptide ligands for the KIX domain of the p300/CBP coactivator. KIX has been the subject of numerous ligand discovery strategies, but potent inhibitors of its interaction with transcription factors remain difficult to access. Although the computational approach

SUBMITTER: Modell AE 

PROVIDER: S-EPMC8959088 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature