Design of HIV protease inhibitors based on inorganic polyhedral metallacarboranes

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

doi:https://dx.doi.org/10.1021/jm9011388

Number of the records: 1

Design of HIV protease inhibitors based on inorganic polyhedral metallacarboranes

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SYSNO ASEP	0332864
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	Design of HIV protease inhibitors based on inorganic polyhedral metallacarboranes
Author(s)	Řezáčová, Pavlína (UOCHB-X)_{RID, ORCID} Pokorná, Jana (UOCHB-X)_RID Brynda, Jiří (UMG-J)_RID Kožíšek, Milan (UOCHB-X)_{RID, ORCID} Cígler, Petr (UOCHB-X)_{RID, ORCID} Lepšík, Martin (UOCHB-X)_{RID, ORCID} Fanfrlík, Jindřich (UOCHB-X)_{RID, ORCID} Řezáč, Jan (UOCHB-X)_{RID, ORCID} Grantz Šašková, Klára (UOCHB-X)_{RID, ORCID} Sieglová, Irena (UMG-J) Plešek, Jaromír (UACH-T) Šícha, Václav (UACH-T)_{RID, ORCID, SAI} Grüner, Bohumír (UACH-T)_{RID, SAI, ORCID} Oberwinkler, H. (DE) Sedláček, Juraj (UMG-J)_RID Kräusslich, H. G. (DE) Hobza, Pavel (UOCHB-X)_{RID, ORCID} Král, V. (CZ) Konvalinka, Jan (UOCHB-X)_{RID, ORCID}
Number of authors	19
Source Title	Journal of Medicinal Chemistry. - : American Chemical Society - ISSN 0022-2623 Roč. 52, č. 22 (2009), s. 7132-7141
Number of pages	10 s.
Language	eng - English
Country	US - United States
Keywords	HIV protease inhibitors ; aspartic proteases ; viral resistance ; cobalt bis(dicarbollide) ; crystal structure
Subject RIV	CC - Organic Chemistry
R&D Projects	IAAX00320901 GA AV ČR - Academy of Sciences of the Czech Republic (AV ČR)
	LC512 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
	LC523 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
CEZ	AV0Z40550506 - UOCHB-X (2005-2011)
	AV0Z50520514 - UMG-J (2005-2011)
	AV0Z40320502 - UACH-T (2005-2011)
UT WOS	000271825600018
DOI	10.1021/jm9011388
Annotation	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.
Workplace	Institute of Organic Chemistry and Biochemistry
Contact	asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Viktorie Chládková, Tel.: 232 002 434
Year of Publishing	2010

Number of the records: 1