Comparison of proline and N‐methylnorleucine induced conformational equilibria in cyclic pentapeptides

Abstract

The cyclic, imido acid containing pentapeptides cyclo(Asp-Trp-(NMe)Nle-Asp-Phe) (cpp[NMeNle3]) and cyclo(Asp-Trp-Pro-Asp-Phe) (cpp[Pro3]) have been investigated by 1H-NMR spectroscopy in DMSO and by restrained molecular dynamics methods. The spectra indicate the existence of at least four cis/trans isomers for cpp[NMeNle3] and two cis/trans isomers for cpp[Pro3]. In addition to the imido peptide bonds, cpp[NMeNle3] shows cis/trans isomerization of the Asp4-Phe5 and Phe5-Asp1 peptide bonds whereas only the Phe5-Asp1 peptide bond isomerizes in the Pro-containing peptide. In cpp[Pro3] all cis bonds are centred in βVIb turns. Also, cpp[NMeNle3] prefers backbone angles around the cis bonds which are rather similar to the angles of a βVIb turn. The higher number of cis/trans isomers and slight deviations in the backbone angles of comparable isomers of both peptides are caused by an enhanced flexibility of cpp[NMeNle3] due to the possibility of the φ-(NMe)Nle rotation