Local versus Global Control of Helical Folding in β‑Peptide Segments Using Hydrazino Turns

Rational control of the self-organization of β-peptides sequences to adopt regular secondary structures is an important challenge in peptidomimetic foldamer science. By replacing the N- and C-terminal residues of homooligomers of trans-2-aminocyclobutanecarboxylic acid (tACBC)n with N-aminoazetidine-2-carboxylic acid, an 8-helical topology is shown to dominate for sequences up to n = 7. This constitutes an atomic-level tool to override locally the preferred global 12-helix secondary structure of the corresponding tACBC homooligomers of the same length.

理性调控β-肽（β-peptides）序列的自组织行为以形成规则二级结构，是拟肽折叠体科学领域的一项重要研究挑战。研究人员将反式-2-氨基环丁烷羧酸（trans-2-aminocyclobutanecarboxylic acid，tACBC）均聚寡肽（(tACBC)ₙ）的N端与C端残基替换为N-氨基氮杂环丁烷-2-羧酸后，发现当序列长度n≤7时，8螺旋拓扑结构成为主导构象。该策略为在原子尺度上局部扭转同等长度对应tACBC均聚寡肽所偏好的全局12螺旋二级结构提供了精准调控手段。