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.