4drq
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 acidExploration 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
Structural highlights
Function[FKBP5_HUMAN] Interacts with functionally mature heterooligomeric progesterone receptor complexes along with HSP90 and TEBP. Publication Abstract from PubMedFK506-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[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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