Conformational Flexibility of Cyclosporins

Authors

  • B. Kratochvil Department of Solid State Chemistry, Institute of Chemical Technology, Prague,
  • M. Husak Department of Solid State Chemistry, Institute of Chemical Technology, Prague,
  • A. Jegorov Galena Co., Research Unit, Ceske Budejovice

Abstract

This review summarizes the present knowledge of conformations of cyclosporins mainly in the solid state. A very small chemical change of the cyclosporin backbone causes a significant change in biological properties. The mechanism of immunosuppressive activity of cyclosporin A is explained on the basis of conformational flexibility of the cyclosporin skeleton. Cyclosporin A adopts three main conformations: the tightly folded one of free cyclosporin in crystals and solution, the open one in the receptor-bound state in cyclosporin complexes with cyclophilin A and the very open one in the cyclosporin-FAB (fragment of antibody) complex. A conformational comparison of variously solvated cyclosporin A with its non-immunosuppressive derivatives (cyclosporins E and H) shows some small differences in the system of intramolecular H-bonds of cyclosporin skeletons. The inclusion effect of packed cyclosporin molecules in crystalline cyclosporin clathrates enables preferential crystallization of cyclosporins with various chiral molecules of organic solvents.

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Published

2001-02-15

How to Cite

Kratochvil, B., Husak, M., & Jegorov, A. (2001). Conformational Flexibility of Cyclosporins. Chemické Listy, 95(1). Retrieved from http://ww-w.chemicke-listy.cz/ojs3/index.php/chemicke-listy/article/view/2451

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