Effect of temperature on molecular structure of cyclosporin A

By reversed-phase HPLC and NMR spectroscopy, cyclosporin A (CsA) was found to have several molecular structures in polar solvents. In addition, temperature change was found to cause the structural alteration in the polypeptide chain of CsA. Although CD spectrum of CsA in ethanol/water was indicative of the beta-turn structure rather than the beta-sheet structure of the polypeptide chain, the temperature-dependent structural changes were undetectable by CD spectroscopy. The inhibitory effect of CsA on peptidyl prolyl cis-trans isomerase activity was suppressed with elevation in temperature. These results indicate that the alteration in the tertiary structure of CsA plays an important role for the binding capability to its receptor and the immunosuppressive activity.