Department of Pharmaceutical Sciences, Northeast Ohio Medical University, Rootstown, 4209 State Route 44, Rootstown, OH 44272, USA.
Bioorg Med Chem Lett. 2011 Sep 15;21(18):5498-501. doi: 10.1016/j.bmcl.2011.06.111. Epub 2011 Jul 2.
A novel outer mitochondrial membrane protein containing [2Fe-2S] clusters, mitoNEET was first identified through its binding to the anti-diabetic drug pioglitazone. Pioglitazone belongs to a family of drugs that are peroxisome proliferator-activated receptor (PPAR) gamma agonists, collectively known as glitazones. With the lack of pharmacological tools available to fully elucidate mitoNEET's function, we developed a binding assay to probe the glitazone binding site with the aim of developing selective and high affinity compounds. We used multiple thiazolidine-2,4-dione (TZD), 2-thioxothiazolidin-4-one (TTD), and 2-iminothiazolidin-4-one (ITD) compounds to establish several trends to enhance ligand development for the purpose of elucidating mitoNEET function.
一种新型的含有[2Fe-2S]簇的线粒体外膜蛋白，mitoNEET 最初是通过与抗糖尿病药物吡格列酮结合而被鉴定出来的。吡格列酮属于过氧化物酶体增殖物激活受体 (PPAR)γ激动剂家族，统称为噻唑烷二酮类药物。由于缺乏药理学工具来充分阐明 mitoNEET 的功能，我们开发了一种结合测定法来探测噻唑烷二酮结合位点，目的是开发具有选择性和高亲和力的化合物。我们使用多种噻唑烷-2,4-二酮 (TZD)、2-硫代噻唑烷-4-酮 (TTD) 和 2-亚氨基噻唑烷-4-酮 (ITD) 化合物来建立了几个增强配体开发的趋势，目的是阐明 mitoNEET 的功能。
