Solvent-dependent conformations of a cyclic tetrapeptide

Abstract

The conformations of cyclo(-γ-Abu-L-Pro-)₂ in several solvents have been characterized by means of ¹H and ¹³C NMR, CD and IR spectra. CD results indicate that the change in polarity of the solvent induces an inversion of the conformation, revealed by the disappearance of the positive peak near 210 nm and then by the gradual appearance of a negative trough near 210 nm having opposite chirality. The data of NMR spectroscopy in CDCl₃, CD₂Cl₂, CD₃OH, (CD₃)₂SO and D₂O indicate that cyclo(-γ-Abu-L-Pro-)₂ has a C₂ symmetric conformation consisting of the cis–trans–cis–trans peptide bond backbone (with two cis γ-Abu-L-Pro bonds) in all solvents, and that the change of polarity of solvent induces the inversion of cis and trans conformations around the Pro ^αC–CO single bond. (The trans and cis regions describe the rotational states of the Pro ^αC–CO single bond in which the Pro ^αC–H is trans and cis to the direction of the Pro carbonyl oxygen atom, respectively). The cis–trans–cis–trans conformation containing the two cis Pro ^αC–CO bonds in CDCl₃ and CD₂Cl₂ is stabilized by the presence of seven-membered rings consisting of intramolecular hydrogen bonds between ^γNH and ^αCO in the γ-Abu residue.