Solvent influence on the conformation of cyclosporin. An FT-IR study

Infrared spectra of the cyclic peptide cyclosporin A and three analogues have been measured in a number of organic solvents (CCl4, CDCl3, acetonitrile, DMSO, and 50:50 acetonitrile:D2O). Seven of the eleven amide groups of cyclosporin A are methylated, the remaining four N-H protons forming strong intramolecular hydrogen bonds in the crystal and in CDCl3 solution. These hydrogen bonds give rise to amide I (C=O stretching) bands at positions characteristic of β-turns, γ-turns, and β-sheet domains in proteins and model polypeptides. Increasing the polarity of the solvent eliminates some of these features; however, the spectra in DMSO and acetonitrile–D2O retain strong amide I absorptions characteristic of hydrogen-bonded carbonyl groups. The conformation of cyclosporin A in water cannot be observed directly due to low solubility; these findings suggest that the structure likely retains strong intramolecular hydrogen bonding. Spectra of the three analogues are consistent with this interpretation. Implication...