Počet záznamů: 1

Design of HIV protease inhibitors based on inorganic polyhedral metallacarboranes

  1. 1.
    0332864 - UOCHB-X 2010 RIV US eng J - Článek v odborném periodiku
    Řezáčová, Pavlína - Pokorná, Jana - Brynda, Jiří - Kožíšek, Milan - Cígler, Petr - Lepšík, Martin - Fanfrlík, Jindřich - Řezáč, Jan - Grantz Šašková, Klára - Sieglová, Irena - Plešek, Jaromír - Šícha, Václav - Grüner, Bohumír - Oberwinkler, H. - Sedláček, Juraj - Kräusslich, H. G. - Hobza, Pavel - Král, V. - Konvalinka, Jan
    Design of HIV protease inhibitors based on inorganic polyhedral metallacarboranes.
    Journal of Medicinal Chemistry. Roč. 52, č. 22 (2009), s. 7132-7141 ISSN 0022-2623
    Grant CEP: GA AV ČR IAAX00320901; GA MŠk LC512; GA MŠk LC523
    GRANT EU: European Commission(XE) 37693 - HIV PI RESISTANCE
    Výzkumný záměr: CEZ:AV0Z40550506; CEZ:AV0Z50520514; CEZ:AV0Z40320502
    Klíčová slova: HIV protease inhibitors * aspartic proteases * viral resistance * cobalt bis(dicarbollide) * crystal structure
    Kód oboru RIV: CC - Organická chemie
    Impakt faktor: 4.802, rok: 2009

    HIV protease (HIV PR) is a primary target for anti-HIV drug design. We have previously identified and characterized substituted metallacarboranes as a new class of HIV protease inhibitors. In a structure guided drug design effort, we connected the two cobalt bis(dicarbollide) clusters with a linker to substituted ammonium group. We explored inhibition properties of these compounds with various substitutions, determined the HIV PR:inhibitor crystal structure, and computationally explored the conformational space of the linker. Our results prove the capacity of linker-substituted dual-cage cobalt bis(dicarbollides) as lead compounds for design of more potent inhibitors of HIV PR.
    Trvalý link: http://hdl.handle.net/11104/0177990