VSE knjižnice (vzajemna bibliografsko-kataložna baza podatkov COBIB.SI)
  • Discovery of d-amino acid oxidase inhibitors based on virtual screening against the lid-open enzyme conformation
    Szilágyi, Bence ...
    D-Amino acid oxidase (DAAO) inhibitors are typically small polar compounds with often suboptimal pharmacokinetic properties. Features of the native binding site limit the operational freedom of ... further medicinal chemistry efforts. We therefore initiated a structure based virtual screening campaign based on the X-ray structures of DAAO complexes where larger ligands shifted the loop (lid opening) covering the native binding site. The virtual screening of our in-house collection followed by the in vitro test of the best ranked compounds led to the identification of a new scaffold with micromolar IC50. Subsequent SAR explorations enabled us to identify submicromolar inhibitors. Docking studies supported by in vitro activity measurements suggest that compounds bind to the active site with a salt-bridge characteristic to DAAO inhibitor binding. In addition, displacement of and interaction with the loop covering the active site contributes significantly to the activity of the most potent compounds.
    Vir: Bioorganic & Medicinal Chemistry Letters. - ISSN 0960-894X (Vol. 28, iss. 10, 2018, str. 1693-1698)
    Vrsta gradiva - članek, sestavni del ; neleposlovje za odrasle
    Leto - 2018
    Jezik - angleški
    COBISS.SI-ID - 4502129

    Povezava(-e):

    https://www.sciencedirect.com/science/article/pii/S0960894X18303603
    DOI

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