Trp-Trp cross-linking: A structure–reactivity relationship in the formation and design of hyperstable peptide β-hairpin and α-helix scaffolds

Abstract

Using model peptide β-hairpin scaffolds, the facile formation of a remarkably stable covalently cross-linked modification is reported in the tryptophan side chain, which confers hyperstability to the scaffold and displays a unique structure–reactivity relationship. This strategy is also validated to obtain a thermostable α-helix. Such imposition of conformational constraints can have versatile applications in peptide-based drug discovery, and this strategy may improve peptide bioavailability.