X-Pro peptides: synthesis and solution conformation of benzyloxycarbonyl-(Aib-Pro)₄methyl ester. Evidence for a novel helical structure

Abstract

The synthesis of the octapeptide, benzyloxycarbonyl-(α-aminoisobutyryl-L-prolyl)₄-methyl ester [Z-(Aib-Pro)₄-OMe] and an analysis of its solution conformation is reported. The octapeptide is shown to possess three strong intramolecular hydrogen bonds on the basis of studies of the solvent and temperature dependence of NH chemical shifts and rates of hydrogen-deuterium exchange. ¹³C studies are consistent with a structure involving only trans Aib-Pro bonds, while ir experiments support a hydrogen-bonded conformation. The Aib 3, 5, and 7 NH groups are shown to participate in hydrogen bonding. A 3₁₀ helical conformation compatible with the spectroscopic data is suggested. The proposed conformation consists of three type III β-turns with Aib and Pro at the corners and stabilized by 4→ 1 intramolecular hydrogen bonds.