4dpf

BACE-1 in complex with a HEA-macrocyclic type inhibitorBACE-1 in complex with a HEA-macrocyclic type inhibitor

Structural highlights 4dpf is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: Related: 4dpi Gene: BACE1, BACE, KIAA1149 (Homo sapiens) Activity: Memapsin 2, with EC number 3.4.23.46 Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed A series of P1-P3 linked macrocyclic BACE-1 inhibitors containing a hydroxyethylamine (HEA) isostere scaffold has been synthesized. All inhibitors comprise a toluene or N-phenylmethanesulfonamide P2 moiety. Excellent BACE-1 potencies, both in enzymatic and cell-based assays, were observed in this series of target compounds, with the best candidates displaying cell-based IC(50) values in the low nanomolar range. As an attempt to improve potency, a phenyl substituent aiming at the S3 subpocket was introduced in the macrocyclic ring. X-ray analyzes were performed on selected compounds, and enzyme-inhibitor interactions are discussed. Highly potent macrocyclic BACE-1 inhibitors incorporating a hydroxyethylamine core: Design, synthesis and X-ray crystal structures of enzyme inhibitor complexes.,Sandgren V, Agback T, Johansson PO, Lindberg J, Kvarnstrom I, Samuelsson B, Belda O, Dahlgren A Bioorg Med Chem. 2012 Jul 15;20(14):4377-89. Epub 2012 May 24. PMID:22698785 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta secretase

spinqualitylabelsall models 4dpf, resolution 1.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image