Toward the Understanding of Immunosuppression

Cyclosporin, FK506, and rapamycin exhibit astounding immunosuppressive effects. The first of these is a cyclic undecapeptide, the second a peptide macrolide. In the cytosol they bind to proteins that exhibit rotamase activity. Presumably, therefore, these immunosuppressives inhibit the ubiquitous rotamases. Much information has been obtained recently on the structures of FK506 and its complex with the FK506 binding protein, and the mechanism of action of these compounds is beginning to emerge. (Figure Presented.)