Stretching Peptides to Generate Small Molecule β-Strand Mimics.

ABSTRACT: Advances in the modulation of protein-protein interactions (PPIs) enable both characterization of PPI networks that govern diseases and design of therapeutics and probes. The shallow protein surfaces that dominate PPIs are challenging to target using standard methods, and approaches for accessing extended backbone structures are limited. Here, we incorporate a rigid, linear, diyne brace between side chains at the i to i+2 positions to generate a family of low-molecular-weight, extended-backbone peptide macrocycles. NMR and density functional theory studies show that these stretched peptides adopt stable, rigid conformations in solution and can be tuned to explore extended peptide conformational space. The diyne brace is formed in excellent conversions (>95%) and amenable to h

SUBMITTER: Adams ZC 

PROVIDER: S-EPMC10141592 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature