The conformational characteristics in solution of the synthetic cyclic hexapeptide 5L-ala-D-ala.

Abstract

AbstractAn attempt to elucidate the solution conformation(s) of the synthetic cyclic hexapeptide 5L‐ala·D‐ala is described. Nuclear magnetic resonance (nmr) spectra are recorded for the purpose of measuring the vicinal coupling constant between the amide and α‐protons in each residue and to observe the deuterium exchange rate and temperature dependence of the chemical shift of each amide proton. Low‐energy cyclic conformations, whose individual residues are in conformations consistent with the observed amide to α‐proton coupling constant, are searched for in an approximate theoretical treatment. The two lowest energy, all trans peptide bond conformations generated are distinguishable by the presence or absence of a single intramolecular hydrogen bond. The observed temperature independence of the chemical shift of one of the amide protons is consistent with the presence of a single intramolecular hydrogen bond, while the observation of similar deuterium exchange rates for each of the amide protons indicates their comparable availability to solvent. Consequently, it is concluded that 5L‐ala·D‐ala is in rapid equilibrium between conformations with and without a single internal hydrogen bond and possesses considerable conformational flexibility in solution.