Identification of small molecules that bind to the mitochondrial protein mitoNEET.

Autor: Geldenhuys WJ; Department of Pharmaceutical Sciences, School of Pharmacy, West Virginia University, 1 Medical Center Drive, Morgantown, WV 26506, USA. Electronic address: werner.geldenhuys@hsc.wvu.edu., Yonutas HM; Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, KY 40536, USA; Anatomy and Neurobiology, University of Kentucky, Lexington, KY 40536, USA., Morris DL; Department of Chemistry and Biochemistry, University of Akron, Akron, OH 44325, USA., Sullivan PG; Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, KY 40536, USA; Anatomy and Neurobiology, University of Kentucky, Lexington, KY 40536, USA., Darvesh AS; Department of Pharmaceutical Sciences, Northeast Ohio Medical University, Rootstown, OH 44240, USA., Leeper TC; Department of Chemistry and Biochemistry, University of Akron, Akron, OH 44325, USA.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2016 Nov 01; Vol. 26 (21), pp. 5350-5353. Date of Electronic Publication: 2016 Sep 06.
DOI: 10.1016/j.bmcl.2016.09.009
Abstrakt: 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.
(Copyright © 2016. Published by Elsevier Ltd.)
Databáze: MEDLINE
Externí odkaz: