A designed β-hairpin peptide

Abstract

A synthetic octapeptide, Boc-Leu-Val-Val-D-Pro-Gly-Leu-Val-Val-OMe (1) has been designed as a model for a β-hairpin conformation. Circular dichroism spectra in various organic solvents reveal a single negative band at 214-217 nm consistent with β-sheet structures. NMR studies in CDCl₃ and C₆D₆ establish the solvent shielded nature of the Leu(1), Val(3), Leu(6) and Val (8) NH groups. Nuclear Overhauser effects are observed between Val(7) C^αH and Val(2) (C^αH) protons providing strong support for a beta-hairpin conformation. Several important diagnostic interresidue NOEs establish a Type II′ β-turn conformation for the D-Pro-Gly segment and extended conformations for the amino and carboxyl terminal tripeptide arms. The high solubility of the β-hairpin peptide in organic solvents holds promise for the development of models for three and four stranded β-sheets.