Combined computational and intracellular peptide library screening: towards a potent and selective Fra1 inhibitor.

ABSTRACT: To date, most research into the inhibition of oncogenic transcriptional regulator, Activator Protein 1 (AP-1), has focused on heterodimers of cJun and cFos. However, the Fra1 homologue remains an important cancer target. Here we describe library design coupled with computational and intracellular screening as an effective methodology to derive an antagonist that is selective for Fra1 relative to Jun counterparts. To do so the isCAN computational tool was used to rapidly screen >75 million peptide library members, narrowing the library size by >99.8% to one accessible to intracellular PCA selection. The resulting 131 072-member library was predicted to contain high quality binders with both a high likelihood of target engagement, while simultaneously avoiding homodimerization and off

SUBMITTER: Yu M 

PROVIDER: S-EPMC8341738 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature