A novel binding assay identifies high affinity ligands to the rosiglitazone binding site of mitoNEET.

A novel binding assay identifies high affinity ligands to the rosiglitazone binding site of mitoNEET.

Geldenhuys Werner J; Funk Max O; Awale Prabha S; Lin Li; Carroll Richard T

Bioorganic & medicinal chemistry letters

2011

2011-09

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

Binding Sites/drug effects; Dose-Response Relationship; Drug; Ligands; Mitochondrial Proteins/*antagonists & inhibitors/metabolism; Molecular Structure; Recombinant Proteins/antagonists & inhibitors/metabolism; Rosiglitazone; Stereoisomerism; Structure-Activity Relationship; Thiazolidinediones/chemical synthesis/chemistry/*pharmacology

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5498–5501

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