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Carborane-containing urea-based inhibitors of glutamate carboxypeptidase II: Synthesis and structural characterization

The result's identifiers

  • Result code in IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F86652036%3A_____%2F15%3A00456306" target="_blank" >RIV/86652036:_____/15:00456306 - isvavai.cz</a>

  • Result on the web

    <a href="http://dx.doi.org/10.1016/j.bmcl.2015.09.062" target="_blank" >http://dx.doi.org/10.1016/j.bmcl.2015.09.062</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.1016/j.bmcl.2015.09.062" target="_blank" >10.1016/j.bmcl.2015.09.062</a>

Alternative languages

  • Result language

    angličtina

  • Original language name

    Carborane-containing urea-based inhibitors of glutamate carboxypeptidase II: Synthesis and structural characterization

  • Original language description

    Glutamate carboxypeptidase II (GCPII) is a zinc metalloprotease on the surface of astrocytes which cleaves N-acetylaspartylglutamate to release N-acetylaspartate and glutamate. GCPII inhibitors can decrease glutamate concentration and play a protective role against apoptosis or degradation of brain neurons. Herein, we report the synthesis and structural analysis of novel carborane-based GCPII inhibitors. We determined the X-ray crystal structure of GCPII in complex with a carborane-containing inhibitorat 1.79 angstrom resolution. The X-ray analysis revealed that the bulky closo-carborane cluster is located in the spacious entrance funnel region of GCPII, indicating that the carborane cluster can be further structurally modified to identify promising lead structures of novel GCPII inhibitors. (C) 2015 Elsevier Ltd. All rights reserved.

  • Czech name

  • Czech description

Classification

  • Type

    J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

  • CEP classification

    FR - Pharmacology and apothecary chemistry

  • OECD FORD branch

Result continuities

  • Project

    Result was created during the realization of more than one project. More information in the Projects tab.

  • Continuities

    I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Others

  • Publication year

    2015

  • Confidentiality

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Data specific for result type

  • Name of the periodical

    Bioorganic and Medicinal Chemistry Letters

  • ISSN

    0960-894X

  • e-ISSN

  • Volume of the periodical

    25

  • Issue of the periodical within the volume

    22

  • Country of publishing house

    GB - UNITED KINGDOM

  • Number of pages

    5

  • Pages from-to

    5232-5236

  • UT code for WoS article

    000364535000044

  • EID of the result in the Scopus database