CONFORMATIONAL-CHANGES IN THE CYCLIC UNDECAPEPTIDE CYCLOSPORINE-INDUCED BY INTERACTION WITH METAL-IONS - AN FTIR STUDY

Infra-red spectra have been measured for the cyclic undecapeptide cycl osporin A (CsA) and three analogues CsC, CsD and CsH in acetonitrile a nd in the presence of 10:1 molar excess of Mg2+, Ca2+, Na+ or Li+ in t he same solvent. Interaction with each of these ions is suggested by m arked changes in band positions over the amide I region (1600-1700 cm- 1). The formation of complexes of cyclosporin with calcium and magnesi um ions is indicated by the presence of C=O stretching bands well outs ide the range normally expected for the amide I absorptions of free pe ptides. Although they share this characteristic, the spectra indicate that the mode and/or strength of Ca2+ binding is quite different from that of Mg2+ binding. In contrast, the two monovalent ions interact wi th CsA, CsC and CsD to yield spectra that are very similar to one anot her. The spectra are consistent with binding of the monovalent ions si multaneously to several carbonyl groups of the loop structure.