Structural highlights
Function
[FKBP5_HUMAN] Interacts with functionally mature heterooligomeric progesterone receptor complexes along with HSP90 and TEBP.
Publication Abstract from PubMed
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Gopalakrishnan R, Kozany C, Wang Y, Schneider S, Hoogeland B, Bracher A, Hausch F. Exploration of Pipecolate Sulfonamides as Binders of the FK506-Binding Proteins 51 and 52. J Med Chem. 2012 Mar 29. PMID:22455398 doi:10.1021/jm201747c
