Structure–Property Relationship Study of N‑(Hydroxy)Peptides for the Design of Self-Assembled Parallel β‑Sheets

The design of novel and functional biomimetic foldamers remains a major challenge in creating mimics of native protein structures. Herein, we report the stabilization of a remarkably short β-sheet by incorporating N-(hydroxy)­glycine (Hyg) residues into the backbone of peptides. These peptide–peptoid hybrids form unique parallel β-sheet structures by self-assembly upon hydrogenation. Our spectroscopic and crystallographic data suggest that the local conformational perturbations induced by N-(hydroxy)­amides are outweighed by a network of strong interstrand hydrogen bonds.设计兼具新颖性与功能性的仿生折叠体（biomimetic foldamers），仍是构建天然蛋白质结构模拟物领域的核心挑战。本文中，我们报道了一种通过将N-（羟基）甘氨酸（N-(hydroxy)glycine，缩写Hyg）残基引入肽骨架，实现对极短β-折叠片（β-sheet）的稳定化策略。这些肽-类肽杂合体（peptide–peptoid hybrids）可在氢化作用下经自组装形成独特的平行β-折叠片结构。我们的光谱学与晶体学数据表明，由N-（羟基）酰胺诱导产生的局部构象扰动，其不利影响可被强大的链间氢键网络所抵消，即后者的作用远胜于前者。