title: A novel binding assay identifies high affinity ligands to the rosiglitazone binding site of mitoNEET.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Sciences, Northeast Ohio Medical University, Rootstown, 4209 State Route 44, Rootstown, OH 44272, USA. wgeldenh@neoucom.edu
authors.forename: Werner J
authors.initials: WJ
authors.lastname: Geldenhuys
authors.forename: Max O
authors.initials: MO
authors.lastname: Funk
authors.forename: Prabha S
authors.initials: PS
authors.lastname: Awale
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.forename: Richard T
authors.initials: RT
authors.lastname: Carroll
mesh_terms: D001665:Binding Sites / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008024:Ligands; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015394:Molecular Structure; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077154:Rosiglitazone; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D045162:Thiazolidinediones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C525595:CISD1 protein, human; D008024:Ligands; D024101:Mitochondrial Proteins; D011994:Recombinant Proteins; D045162:Thiazolidinediones; D000077154:Rosiglitazone