6eb2 | pdb_00006eb2

HIV-1 Integrase Catalytic Core Domain Complexed with Allosteric Inhibitor (2S)-[1-(1-benzyl-1H-pyrazol-4-yl)-3-(3,4-dihydro-2H-1-benzopyran-6-yl)isoquinolin-4-yl](tert-butoxy)acetic acid

spinqualitylabelsall models 6eb2, resolution 2.49Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6eb2 is a 1 chain structure with sequence from 9hiv1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: J3P NonStd Res: CAF Gene: pol (9HIV1) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed Allosteric HIV-1 integrase inhibitors (ALLINIs) are a new class of potential antiretroviral therapies with a unique mechanism of action and drug resistance profile. To further extend this class of inhibitors via a scaffold hopping approach, we have synthesized a series of analogues possessing an isoquinoline ring system. Lead compound 6l binds in the v-shaped pocket at the IN dimer interface and is highly selective for promoting higher-order multimerization of inactive IN over inhibiting IN-LEDGF/p75 binding. Importantly, 6l potently inhibited HIV-1NL4-3 (A128T IN), which confers marked resistance to archetypal quinoline-based ALLINIs. Thermal degradation studies indicated that at elevated temperatures the acetic acid side chain of specific isoquinoline derivatives undergo decarboxylation reactions. This reactivity has implications for the synthesis of various ALLINI analogues. An Isoquinoline Scaffold as a Novel Class of Allosteric HIV-1 Integrase Inhibitors.,Wilson TA, Koneru PC, Rebensburg SV, Lindenberger JJ, Kobe MJ, Cockroft NT, Adu-Ampratwum D, Larue RC, Kvaratskhelia M, Fuchs JR ACS Med Chem Lett. 2019 Jan 30;10(2):215-220. doi:, 10.1021/acsmedchemlett.8b00633. eCollection 2019 Feb 14. PMID:30783506 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Retroviral integrase 3D structures

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