Design of HIV protease inhibitors based on inorganic polyhedral metallacarboranes

0332864 - ÚOCHB 2010 RIV US eng J - Journal Article
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. E-ISSN 1520-4804
R&D Projects: GA AV ČR IAAX00320901; GA MŠMT LC512; GA MŠMT LC523
EU Projects: European Commission(XE) 37693 - HIV PI RESISTANCE
Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z50520514; CEZ:AV0Z40320502
Keywords : HIV protease inhibitors * aspartic proteases * viral resistance * cobalt bis(dicarbollide) * crystal structure
Subject RIV: CC - Organic Chemistry
Impact factor: 4.802, year: 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.
Permanent Link: http://hdl.handle.net/11104/0177990