Mammalian display screening of diverse cystine-dense peptides for difficult to drug targets.

ABSTRACT: Protein:protein interactions are among the most difficult to treat molecular mechanisms of disease pathology. Cystine-dense peptides have the potential to disrupt such interactions, and are used in drug-like roles by every clade of life, but their study has been hampered by a reputation for being difficult to produce, owing to their complex disulfide connectivity. Here we describe a platform for identifying target-binding cystine-dense peptides using mammalian surface display, capable of interrogating high quality and diverse scaffold libraries with verifiable folding and stability. We demonstrate the platform's capabilities by identifying a cystine-dense peptide capable of inhibiting the YAP:TEAD interaction at the heart of the oncogenic Hippo pathway, and possessing the potency and stabi

SUBMITTER: Crook ZR 

PROVIDER: S-EPMC5740061 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature