Macrocyclization of an all-d linear α-helical peptide imparts cellular permeability.

ABSTRACT: Peptide-based molecules hold great potential as targeted inhibitors of intracellular protein-protein interactions (PPIs). Indeed, the vast diversity of chemical space conferred through their primary, secondary and tertiary structures allows these molecules to be applied to targets that are typically deemed intractable via small molecules. However, the development of peptide therapeutics has been hindered by their limited conformational stability, proteolytic sensitivity and cell permeability. Several contemporary peptide design strategies are aimed at addressing these issues. Strategic macrocyclization through optimally placed chemical braces such as olefinic hydrocarbon crosslinks, commonly referred to as staples, may improve peptide properties by (i) restricting conformational fre

SUBMITTER: Kannan S 

PROVIDER: S-EPMC7441689 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature