Peptide-based inhibitors of protein-protein interactions: biophysical, structural and cellular consequences of introducing a constraint.

ABSTRACT: Protein-protein interactions (PPIs) are implicated in the majority of cellular processes by enabling and regulating the function of individual proteins. Thus, PPIs represent high-value, but challenging targets for therapeutic intervention. The development of constrained peptides represents an emerging strategy to generate peptide-based PPI inhibitors, typically mediated by α-helices. The approach can confer significant benefits including enhanced affinity, stability and cellular penetration and is ingrained in the premise that pre-organization simultaneously pays the entropic cost of binding, prevents a peptide from adopting a protease compliant β-strand conformation and shields the hydrophilic amides from the hydrophobic membrane. This conceptual blueprint for the empirical design of pept

SUBMITTER: Wang H 

PROVIDER: S-EPMC8098664 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature