Probing immunosuppressant action with a nonnatural immunophilin ligand

Barbara E. Bierer, Patricia K. Somers, Thomas J. Wandless, Steven J. Burakoff, Stuart L. Schreiber

Research output: Contribution to journalArticlepeer-review

299 Scopus citations


The immunosuppressants FK506 and rapamycin bind to the same immunophilin, FK506 binding protein (FKBP), and inhibit distinct signal transduction pathways in T lymphocytes. A nonnatural immunophilin ligand, 506BD, which contains only the common structural elements of FK506 and rapamycin, was synthesized and found to be a high-affinity ligand of FKBP and a potent inhibitor of FKBP rotamase activity. Whereas 506BD does not interfere with T cell activation, it does block the immunosuppressive effects of both FK506 and rapamycin. Thus, the common immunophilin binding element of these immunosuppressants, which is responsible for rotamase inhibition, is fused to different effector elements, resulting in the inhibition of different signaling pathways. Inhibition of rotamase activity is an insufficient requirement for mediating these effects.

Original languageEnglish
Pages (from-to)556-559
Number of pages4
Issue number4980
StatePublished - 1990
Externally publishedYes


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