Effect of solvent on the cis– trans conformational equilibrium of a proline imide bond of short model peptides in solution

Abstract

Proton NMR spectra of proline-containing short peptides with N-terminal sequences of N-acetyl-prolyl- (Ac-Pro-) N- tert-butoxycarbonyl-phenylalanyl-prolyl- (Boc-Phe-Pro-) and N- tert-butoxycarbonyl-leucyl-prolyl- (Boc-Leu-Pro-) were measured in mixed solvents of hexadeuterodimethylsulfoxide and deuterochloroform (CDCl 3). Population ratios of cis and trans conformers with respect to the proline imide bond and chemical shifts of NH protons were obtained as a function of a CDCl 3 fraction of solvent. With increasing fraction of CDCl 3, the trans percentages of the Ac-Pro- imide bonds increased. On the other hand, those of Boc-Phe-Pro- decreased, and those of Boc-Leu-Pro- exhibited middle tendency. From the solvent-dependent variation of the chemical shifts of the NH protons, intramolecular hydrogen bonds that stabilize the trans form of Ac-Pro- and the cis form of Boc-Phe-Pro- were discussed. For the Ac-Pro- peptides, only the trans forms are found to the compatible with 7-, 10-, and 13-membered hydrogen-bonded rings that would be similar to the ordinary secondary structures, γ- and β-turns and α-helix, respectively. For the cis form of Boc-Phe-Pro-R (R=O-methyl or glycyl-O-ethyl), the hydrogen-bonded structure is found to be similar to the type-VIa β-turn. On the other hand, for Boc-Phe-Pro-Pro-Leu-Gly-NH 2, it has been suggested that two different hydrogen bonds, which are different from that of the type-VIa β-turn, support each other and cooperatively stabilize the cis form.