A DESIGNED BETA-HAIRPIN PEPTIDE

A synthetic octapeptide, Boc-Leu-Val-Val-D-Pro-Gly-Leu-Val-Val-OMe (1) has been designed as a model for a beta P-hairpin conformation. Circular dichroism spectra in various organic solvents reveal a single negative band at 214-217 nm consistent with beta-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) (CH)-H-alpha and Val(2) (CH)-H-alpha protons providing strong support for a beta-hairpin conformation. Several important diagnostic interresidue NOEs establish a Type II' beta-turn conformation for the D-Pro-Gly segment and extended conformations for the amino and carboxyl terminal tripeptide arms. The high solubility of the beta-hairpin peptide in organic solvents holds promise for the development of models for three and four stranded beta-sheets. (C) 1995 Academic Press, Inc.