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|4drq, resolution 1.00Å ()|
|Gene:||AIG6, FKBP5, FKBP51 (Homo sapiens)|
|Related:||4drk, 4drm, 4drn, 4dro, 4drp|
Exploration of Pipecolate Sulfonamides as Binders of the FK506-Binding Proteins 51 and 52: Complex of FKBP51 with 2-(3-((R)-1-((S)-1-(3,5-dichlorophenylsulfonyl)piperidine-2-carbonyloxy)-3-(3,4-dimethoxy -phenyl)propyl)phenoxy)acetic acid
FK506-binding proteins (FKBP) 51 and 52 are co-chaperones that modulate the signal transduction of steroid hormone receptors. Single nucleotide polymorphisms in the gene encoding FKBP51 have been associated with a variety of psychiatric disorders. Rapamycin and FK506 are two macrocyclic natural products, which tightly bind to all these proteins. A bio-isosteric replacement of the alpha-ketoamide moiety of rapamycin and FK506 with a sulfonamide was envisaged with the retention of the conserved hydrogen bonds. A focused solid support-based synthesis protocol was developed, which led to ligands with submicromolar affinity for FKBP51 and FKBP52. The molecular binding mode for one sulfonamide analog was confirmed by X-ray crystallography.
Exploration of Pipecolate Sulfonamides as Binders of the FK506-Binding Proteins 51 and 52., Gopalakrishnan R, Kozany C, Wang Y, Schneider S, Hoogeland B, Bracher A, Hausch F, J Med Chem. 2012 Mar 29. PMID:22455398
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.