2xni

Protein-ligand complex of a novel macrocyclic HCV NS3 protease inhibitor derived from amino cyclic boronates

spinqualitylabelsall models 2xni, resolution 3.30Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2xni is a 4 chain structure with sequence from Hepatitis c virus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: MG, TR8, ZN Related: 2xcf, 2xcn Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed A novel series of P2-P4 macrocyclic HCV NS3/4A protease inhibitors with alpha-amino cyclic boronates as warheads at the P1 site was designed and synthesized. When compared to their linear analogs, these macrocyclic inhibitors exhibited a remarkable improvement in cell-based replicon activities, with compounds 9a and 9e reaching sub-micromolar potency in replicon assay. The SAR around alpha-amino cyclic boronates clearly established the influence of ring size, chirality and of the substitution pattern. Furthermore, X-ray structure of the co-crystal of inhibitor 9a and NS3 protease revealed that Ser-139 in the enzyme active site traps boron in the warhead region of 9a, thus establishing its mode of action. Novel macrocyclic HCV NS3 protease inhibitors derived from alpha-amino cyclic boronates.,Li X, Zhang YK, Liu Y, Ding CZ, Zhou Y, Li Q, Plattner JJ, Baker SJ, Zhang S, Kazmierski WM, Wright LL, Smith GK, Grimes RM, Crosby RM, Creech KL, Carballo LH, Slater MJ, Jarvest RL, Thommes P, Hubbard JA, Convery MA, Nassau PM, McDowell W, Skarzynski TJ, Qian X, Fan D, Liao L, Ni ZJ, Pennicott LE, Zou W, Wright J Bioorg Med Chem Lett. 2010 Oct 1;20(19):5695-700. Epub 2010 Aug 10. PMID:20801653 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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