TY - JOUR
T1 - Probing immunosuppressant action with a nonnatural immunophilin ligand
AU - Bierer, Barbara E.
AU - Somers, Patricia K.
AU - Wandless, Thomas J.
AU - Burakoff, Steven J.
AU - Schreiber, Stuart L.
PY - 1990
Y1 - 1990
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0025226638&partnerID=8YFLogxK
U2 - 10.1126/science.1700475
DO - 10.1126/science.1700475
M3 - Article
C2 - 1700475
AN - SCOPUS:0025226638
SN - 0036-8075
VL - 250
SP - 556
EP - 559
JO - Science
JF - Science
IS - 4980
ER -