Abstract:
:The immunosuppressive agent FK-506 has received much attention due to its efficacy and potency in the areas of transplant rejection and autoimmune disease. Calcineurin, a Ca(2+)-calmodulin activated phosphatase, was recently implicated in the immunosuppressive mechanism of FK-506. In our ongoing search for superior immunosuppressive agents, we have synthesized several analogues of FK-506 and tested their mechanistic and immunosuppressive actions. It was found that C-18 hydroxyl analogues of ascomycin, an analogue of FK-506 also called FR900520, bound tightly to immunophilin FKBP-12, but do not show any immunosuppressive activity in vitro or in vivo despite good bioavailability. Further, they reverse the inhibition of calcineurin caused by FK-506/FKBP-12 complex.
journal_name
FEBS Lettjournal_title
FEBS lettersauthors
Kawai M,Lane BC,Hsieh GC,Mollison KW,Carter GW,Luly JRdoi
10.1016/0014-5793(93)81196-7subject
Has Abstractpub_date
1993-01-25 00:00:00pages
107-13issue
2eissn
0014-5793issn
1873-3468pii
0014-5793(93)81196-7journal_volume
316pub_type
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