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Cyclophilin binds to the region of cyclosporine involved in its immunosuppressive activity

✍ Scribed by Valérie F. J. Quesniaux; Max H. Schreier; Roland M. Wenger; Peter C. Hiestand; Matthew W. Harding; Marc H. V. Van Regenmortel

Publisher
John Wiley and Sons
Year
1987
Tongue
English
Weight
784 KB
Volume
17
Category
Article
ISSN
0014-2980

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✦ Synopsis

Although several cytosolic proteins including calmodulin and cyclophilin have been shown to bind cyclosporine, the direct involvement of these proteins in the immunosuppressive activity of cyclosporine remains to be established. In the present study, a quantitative immunoassay for cyclophilin was developed which made it possible to compare its relative affinity for cyclosporine and any of its analogues. The binding of cyclophilin to cyclosporine coated on a solid phase was revealed by anticyclophilin rabbit antiserum followed by antiglobulin-enzyme conjugate. This reaction could be inhibited by addition of free cyclosporine or certain cyclosporine analogues. By studying the binding of cyclophilin to more than fifty cyclosporine derivatives modified singly on each of the eleven amino acid residues, it could be shown that cyclophilin binds to the residues of cyclosporine known to be critical for its immunosuppressive activity. These data identify cyclophilin as a highly discriminating stereospecific binding protein for cyclosporine.

* This work was carried out during a stay of V. Q.

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