Conformational flexibility of cyclosporins

This review summarizes the present knowledge of conformations of cyclospori ns mainly in the solid state. A very small chemical change of the cyclospor in backbone causes a significant change in biological properties. The mecha nism of immunosuppressive activity of cyclosporin A is explained on the bas is of conformational flexibility of the cyclosporin skeleton. Cyclosporin A adopts three main conformations: the tightly folded one of free cyclospori n in crystals and solution, the open one in the receptor-bound state in cyc losporin complexes with cyclophilin A and the very open one in the cyclospo rinFAB (fragment of antibody) complex. A conformational comparison of vario usly solvated cyclosporin A with its nonimmunosuppressive derivatives (cycl osporins E and H) shows some small differences in the system of intramolecu lar H-bonds of cyclosporin skeletons. The inclusion effect of packed cyclos porin molecules in crystalline cyclosporin clathrates enables preferential crystallization of cyclosporins with various chiral molecules of organic so lvents.