Consequences of Peptide Macrocyclization Revealed by Virus-Inspired β-Hairpin Mimetics.

ABSTRACT: Mimicry of protein secondary structure elements, such as α-helices and β-sheets, using conformationally constrained peptide macrocycles, can be utilized to disrupt native protein-protein and protein-nucleic acid interactions. Although α-helical stapled peptides have been extensively studied as pharmacological probes, the application of β-sheet and β-hairpin mimetics remains comparatively limited. Less is known about the structural and biophysical consequences of β-hairpin macrocyclization in the context of target binding. In this work, we use a poxvirus immune antagonist protein 018 as a template for the structure-based design of β-hairpin mimetic macrocyclic peptides targeting the STAT1 transcription factor. We demonstrate that successive orthogonal cyclizations have additive effects on t

SUBMITTER: Bula AL 

PROVIDER: S-EPMC12813973 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature