Programmable Helicity and Macrocycle Symmetry in β-Peptides via Site-Selective Thioamide Substitution.

ABSTRACT: Thioamides─minimalist amide isosteres in which sulfur replaces the backbone carbonyl oxygen─offer a precise means to modulate peptide conformation through altered hydrogen-bond geometry and polarity. This work presents a general and experimentally validated strategy for programming β-peptide secondary structure with atomic precision, using site-selective thioamide substitution as a minimalist backbone modification. While thioamides have been studied individually, their positional control within β-peptides to direct helicity, curvature, and topology has not been achieved before. Using trans-2-aminocyclopentanecarboxylic acid (ACPC) foldamers as a model system, we show that strategic thioamide placement enables hybrid 12/8-helices, backbone-encoded curvature, and conical 16/12-helices

SUBMITTER: Hong J 

PROVIDER: S-EPMC12679621 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature