Počet záznamů: 1

Structure-Aided Design of Novel Inhibitors of HIV Protease Based on a Benzodiazepine Scaffold

SYSNO ASEP	0385940
Druh ASEP	J - Článek v odborném periodiku
Zařazení RIV	J - Článek v odborném periodiku
Poddruh J	Článek ve WOS
Název	Structure-Aided Design of Novel Inhibitors of HIV Protease Based on a Benzodiazepine Scaffold
Tvůrce(i)	Schimer, Jiří (UOCHB-X)_{RID, ORCID} Cígler, Petr (UOCHB-X)_{RID, ORCID} Veselý, J. (CZ) Grantz Šašková, Klára (UOCHB-X)_{RID, ORCID} Lepšík, Martin (UOCHB-X)_{RID, ORCID} Brynda, Jiří (UMG-J)_RID Řezáčová, Pavlína (UOCHB-X)_{RID, ORCID} Kožíšek, Milan (UOCHB-X)_{RID, ORCID} Císařová, I. (CZ) Oberwinkler, H. (DE) Kraeusslich, H. G. (DE) Konvalinka, Jan (UOCHB-X)_{RID, ORCID}
Celkový počet autorů	12
Zdroj.dok.	Journal of Medicinal Chemistry. - : American Chemical Society - ISSN 0022-2623 Roč. 55, č. 22 (2012), s. 10130-10135
Poč.str.	6 s.
Jazyk dok.	eng - angličtina
Země vyd.	US - Spojené státy americké
Klíč. slova	HIV protease inhibitor ; rational drug design ; 1,4-benzodiazepines
Vědní obor RIV	CE - Biochemie
CEP	GBP208/12/G016 GA ČR - Grantová agentura ČR
	GAP207/11/1798 GA ČR - Grantová agentura ČR
CEZ	AV0Z40550506 - UOCHB-X (2005-2011)
	AV0Z50520514 - UMG-J (2005-2011)
UT WOS	000311461500059
DOI	10.1021/jm301249q
Anotace	HIV protease is a primary target for the design of virostatics. Screening of libraries of non-peptide low molecular weight compounds led to the identification of several new compounds that inhibit HIV PR in the low micromolar range. X-ray structure of the complex of one of them, a dibenzo[b,e][1,4]diazepinone derivative, showed that two molecules of the inhibitor bind to the PR active site. Covalent linkage of two molecules of such a compound by a two carbon linker led to a decrease of the inhibition constant of the resulting compound by 3 orders of magnitude. Molecular modeling shows that these dimeric inhibitors form two crucial hydrogen bonds to the catalytic aspartates that are responsible for their improved activity compared to the monomeric parental building blocks. Dibenzo[b,e][1,4]diazepinone analogues might represent a potential new class of HIV PIs.
Pracoviště	Ústav organické chemie a biochemie
Kontakt	asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Viktorie Chládková, Tel.: 232 002 434
Rok sběru	2013

Počet záznamů: 1