INTERACTION OF TACROLIMUS (FK506) AND ITS METABOLITES WITH FKBP AND CALCINEURIN

被引：47

作者：

TAMURA, K ^{[1
]}

FUJIMURA, T ^{[1
]}

IWASAKI, K ^{[1
]}

SAKUMA, S ^{[1
]}

FUJITSU, T ^{[1
]}

NAKAMURA, K ^{[1
]}

SHIMOMURA, K ^{[1
]}

KUNO, T ^{[1
]}

TANAKA, C ^{[1
]}

KOBAYASHI, M ^{[1
]}

机构：

[1] KOBE UNIV,SCH MED,CHUO KU,KOBE 655,JAPAN

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 1994年 / 202卷 / 01期

关键词：

D O I：

10.1006/bbrc.1994.1947

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Tacrolimus(FK506) is a strong immuno-suppressant and shows its activity through inhibiting IL-2 mRNA transcription by forming pentameric complex with intracellular receptor(FK506 binding protein 12 KDa or FKBP12), Ca2+, calmodulin, and calcineurin. Here, we report the binding activity to FKBP12, the pentameric complex formation and Con-A response inhibiting activities of 7 metabolites. C15-demethylated metabolite(M-3) needed higher quantity to compete in Con-A assay and in pentamer formation assay, although it binds more strongly to FKBP12. The result suggests that the ability to form a pentameric complex is not a two step reaction with the first binding to FKBP12, but a single step reaction by components for the pentamer formation. (C) 1994 Academic Press, Inc.

引用

页码：437 / 443

页数：7

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