Inhibition of O-GlcNAcase by PUGNAc is dependent upon the oxime stereochemistry.
Inhibition of O-GlcNAcase by PUGNAc is dependent upon the oxime stereochemistry.
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PUGNAc 对 O-GlcNAcase 的抑制取决于肟立体化学。
DOI：
10.1016/j.bmc.2005.09.013
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发表时间：
2006
影响因子：
3.5
通讯作者：
Hanover,JohnA
中科院分区：
文献类型：
--
作者：
Perreira,Melissa;Kim,EunJu;Thomas,CraigJ;Hanover,JohnA
合成了一种高效的O-GlcNAcase抑制剂PUGNAc，并分离、定义了两个基于肟基的E和Z立体化学的异构体，并对其活性进行了测试。为了确定每种形式的PUGNAc的正确立体化学指定，对几条证据进行了审查。Z立体异构体进行Beckmann重排的能力最终是最确凿的证据。通过体外和完整的细胞实验确定，PUGNAc的Z型比E型对O-GlcNAcase的抑制作用要强得多。
The potent O-GlcNAcase inhibitor PUGNAc was synthesized and two isomers based on the E and Z stereochemistry of the oxime moiety were separated, defined, and tested for activity. Several lines of evidence were examined in an effort to define the correct stereochemical assignments of each form of PUGNAc. The ability of the Z stereoisomer to undergo the Beckmann rearrangement was ultimately the most definitive proof. It was determined via both in vitro and intact cell experiments that the Z form of PUGNAc was vastly more potent an inhibitor of O-GlcNAcase than the E form.