Conformational properties of hybrid peptides containing α- and ω-amino acids

Abstract

This review briefly surveys the conformational properties of guest ω-amino acid residues when incorporated into host β-peptide sequences. The results presented focus primarily on the use of β- and γ-residues in αω sequences. The insertion of additional methylene groups into peptide backbones enhances the range of accessible conformations, introducing additional torsional variables. A nomenclature system, which permits ready comparisons between α-peptides and hybrid sequences, is defined. Crystal structure determination of hybrid peptides, which adopt helical and β-hairpin conformations permits the characterization of backbone conformational parameters for β- and γ-residues inserted into regular α-polypeptide structures. Substituted β- and γ-residues are more limited in the range of accessible conformation than their unsubstituted counterparts. The achiral β,β-disubstituted γ-amino acid, gabapentin, is an example of a stereochemically constrained residue in which the torsion angles about the C^β-C^γ (θ₁) and C^α-C^β (θ₂) bonds are restricted to the gauche conformation. Hybrid sequences permit the design of novel hydrogen bonded rings in peptide structures.