Identification of small molecules that bind to the mitochondrial protein mitoNEET
Identification of small molecules that bind to the mitochondrial protein mitoNEET
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DOI：
10.1016/j.bmcl.2016.09.009
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发表时间：
2016-11-01
影响因子：
2.7
通讯作者：
Leeper, Thomas C.
中科院分区：
文献类型：
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作者：
Geldenhuys, Werner J.;Yonutas, Heather M.;Leeper, Thomas C.
MitoNEET（CISD 1）是属于锌指蛋白家族的2Fe-2S铁硫簇蛋白。最近，mitoNEET已被证明是与代谢型疾病（如肥胖和癌症）相关的线粒体功能的主要参与者。抗糖尿病药物吡格列酮和罗格列酮是第一个被鉴定的mitoNEET配体。由于对配体与mitoNEET结合的结构要求知之甚少，我们筛选了一小组化合物以深入了解这些要求。我们发现，罗格列酮中的噻唑烷二酮（TZD）弹头并不是与mitoNEET结合的绝对必要条件。这些结果将有助于开发可用于治疗多种疾病中的线粒体功能障碍的新型化合物。(C)2016由Elsevier Ltd.出版
MitoNEET (CISD1) is a 2Fe-2S iron-sulfur cluster protein belonging to the zinc-finger protein family. Recently mitoNEET has been shown to be a major role player in the mitochondrial function associated with metabolic type diseases such as obesity and cancers. The anti-diabetic drug pioglitazone and rosiglitazone were the first identified ligands to mitoNEET. Since little is known about structural requirements for ligand binding to mitoNEET, we screened a small set of compounds to gain insight into these requirements. We found that the thiazolidinedione (TZD) warhead as seen in rosiglitazone was not an absolutely necessity for binding to mitoNEET. These results will aid in the development of novel compounds that can be used to treat mitochondrial dysfunction seen in several diseases. (C) 2016 Published by Elsevier Ltd.