Design and Synthesis of Crosslinked Helix Dimers as Protein Tertiary Structure Mimics.

ABSTRACT: Crosslinked helix dimers (CHDs) are synthetic tertiary helical structure motifs designed to modulate interactions of proteins with binding partners. Helix dimers serve as mimics of coiled coils, which are known to be implicated in a multitude of protein complexes. Coiled coils are typically stable in long peptides (>21-28 residues), because sufficient intra- and interstrand contacts are not available in short peptides to coax strand assembly. To engineer conformationally stable CHDs in short sequences, we introduced a covalent linkage in place of an interhelical salt bridge and sculpted the helical interface with optimal hydrophobic packing. CHDs have shown efficacy for the disruption of targeted protein-protein interactions in biochemical, cellular, and animal models. This article describ

SUBMITTER: Hong SH 

PROVIDER: S-EPMC8740631 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature