Stabilization of β-turn conformations in Pro-X sequences by disulphide bridging. Synthesis and solution conformations of five cyclic cystine peptides

Abstract

Five cyclic peptide disulphides of the type Image have been synthesized, where X = Gly (1), L-Ala (2), D-Ala (3), Aib (4) and L-Leu (5). ¹H NMR studies at 270 MHz in CDCl₃ and (CD₃)₂SO provide evidence of a Pro-X β-turn conformation, stabilized by a transannular 4→1 hydrogen bond involving the Cys(4) NH, in all the peptides. In addition peptides 2, 4 and 5 also possess a second intramolecular hydrogen bond involving the -NHMe group. The spectroscopic data are consistent with a consecutive type III β-turn conformation for peptides 2, 4 and 5, a type I(III) β-turn structure for 1 and a type II turn for 3.