The design, synthesis, and biological evaluation of analogues of the serine-threonine protein phosphatase 1 and 2A selective inhibitor microcystin LA: Rational modifications imparting PP1 selectivity

被引：40
|
作者：
Aggen, JB
Humphrey, JM
Gauss, CM
Huang, HB
Nairn, AC
Chamberlain, AR [1 ]
机构：
[1] Univ Calif Irvine, Dept Chem, Irvine, CA 92697 USA
[2] Chu Tzi Coll Med, Inst Biochem, Iwaki, Fukushima 970, Japan
[3] Rockefeller Univ, New York, NY 10021 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY | 1999年 / 7卷 / 03期
关键词：
microcystin; inhibitor; PP1; PP2A; selective;
D O I：
10.1016/S0968-0896(98)00254-5
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：
Based on the results from previously reported molecular modeling analyses of the interactions between the inhibitor microcystin and the serine-threonine protein phosphatases 1 and 2A, we have designed analogues of microcystin LA with structural modifications intended to impart PP1 selectivity. The synthesis of several first generation analogues followed by inhibition assays revealed that all three are PP1-selective, as predicted. Although the observed selectivities are modest, one of the designed analogues is more selective for PP1 than any known small molecule inhibitor. (C) 1999 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码：543 / 564
页数：22
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