Fundamental role of the fostriecin unsaturated lactone and implications for selective protein phosphatase inhibition
Fundamental role of the fostriecin unsaturated lactone and implications for selective protein phosphatase inhibition
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DOI：
10.1021/ja038672n
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发表时间：
2003-12-24
影响因子：
15
通讯作者：
Boger, DL
中科院分区：
文献类型：
--
作者：
Buck, SB;Hardouin, C;Boger, DL
Key derivatives and analogues of fostriecin were prepared and examined that revealed a fundamental role for the unsaturated lactone and confirmed the essential nature of the phosphate monoester. Thus, an identical 200-fold reduction in protein phosphatase 2A (PP2A) inhibition is observed with either the saturated lactone (7) or with an analogue that lacks the entire lactone (15). This 200-fold increase in PP2A inhibition attributable to the unsaturated lactone potentially may be due to reversible C269 alkylation within the PP β12−β13 active site loop accounting for PP2A/4 potency and selectivity.
