Solvent-induced conformational changes in cyclic peptides: a vibrational circular dichroism study

The three-dimensional structure of a peptide is strongly influenced by its solvent environment. In the present study, we study three cyclic tetrapeptides which serve as model peptides for beta-turns. They are of the general structurecyclo (Boc-Cys-Pro-X-Cys-OMe) with the amino acid X being either glycine (1), or L-or D-leucine (L-or D-2). Using vibrational circular dichroism (VCD) spectroscopy, we confirm previous NMR results which showed that D-2 adopts predominantly a beta(II) turn structure in apolar and polar solvents. Our results for L-2 indicate a preference for a beta(I) structure over beta(II). With increasing solvent polarity, the preference for 1 is shifted from beta(II) towards beta(I). This conformational change goes along with the breaking of an intramolecular hydrogen bond which stabilizes the beta(II) conformation. Instead, a hydrogen bond with a solvent molecule can stabilize the beta(I) turn conformation.