Cleavage of the cyclohexyl-subunit of rapamycin results in loss of immunosuppressive activity.
The cyclohexyl-subunit of rapamycin was cleaved by a sequence involving a Baeyer-Villiger reaction and acid hydrolysis of the resulting lactone-acetal as key steps. Binding of this new rapamycin derivative to FKBP12 was only slightly reduced by this modification, whereas the loss of antiproliferative and immunosuppressive activity was dramatic. These findings indicate that part of the cyclohexyl-subunit of rapamycin could belong to its effector domain.
Sedrani
R
R
Novartis Pharma AG, Preclinical Research, Basel, Switzerland. richard.sedrani@pharma.novartis.com
Jones
L H
LH
Jutzi-Eme
A M
AM
Schuler
W
W
Cottens
S
S
D002999:Clone Cells; D006868:Hydrolysis; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D007959:Lymphocyte Culture Test, Mixed; D020123:Sirolimus / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology
D007166:Immunosuppressive Agents; D020123:Sirolimus