An Enantiodefined Conformationally Constrained Fatty Acid Mimetic and Potent Inhibitor of ToxT.
An Enantiodefined Conformationally Constrained Fatty Acid Mimetic and Potent Inhibitor of ToxT.
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一种对映体构象受限的脂肪酸模拟物和 ToxT 的有效抑制剂。
DOI：
10.1021/acsmedchemlett.1c00378
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发表时间：
2021
影响因子：
4.2
通讯作者：
Micalizio,GlennC
中科院分区：
文献类型：
--
作者：
Markham,LaurenE;Tolbert,JessicaD;Kull,FJon;Midgett,CharlesR;Micalizio,GlennC
棕榈油酸与霍乱弧菌毒力基因的主调控子ToxT结合时所呈现的手性构象，被用来设计一类新的脂肪酸模拟物。最好的模拟物，基于手性氢化物，被发现是这一目标的有效抑制剂。能够进行这些研究的合成化学是基于立体选择性环状交叉偶联反应和溶解金属还原的顺序使用来分别建立C13和C9立体中心的。
The chiral conformation that palmitoleic acid takes when it is bound to ToxT, the master regulator of virulence genes in the bacterial pathogenVibrio cholerae, was used as inspiration to design a novel class of fatty acid mimetics. The best mimetic, based on a chiral hydrindane, was found to be a potent inhibitor of this target. The synthetic chemistry that enabled these studies was based on the sequential use of a stereoselective annulative cross-coupling reaction and dissolving metal reduction to establish the C13 and C9 stereocenters, respectively.