Structure-function relationship of immunosuppressive drugs: A cautionary tale

✍ Scribed by Laurence A. Turka; Craig B. Thompson

• Publisher: John Wiley and Sons
• Year: 1991
• Tongue: English
• Weight: 395 KB
• Volume: 14
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840140326

✦ Synopsis

The immunosuppressants FKSO6 and rapamycin bind to the same immunophilin, FKS06 binding protein (FKBP), and inhibit distinct signal transduction pathways in T lymphocytes. A nonnatural immunophilin ligand, S06BD, which contains only the common structural elements of FKSO6 and rapamycin, was synthesized and found to be a high-afhity ligand of FKBP and a potent inhibitor of FKBP rotamase activity. Whereas 506BD does not interfere with T cell activation, it d m block the immunosuppressive effects of both F-6 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.

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