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

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An Entity of Type : http://linked.opendata.cz/ontology/domain/vavai/Vysledek, within Data Space : linked.opendata.cz associated with source document(s)

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rdf:type	skos:Concept http://linked.opendata.cz/ontology/domain/vavai/Vysledek
rdfs:seeAlso	http://dx.doi.org/10.1021/jm301249q
Description	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. 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. (en)
Title	Structure-Aided Design of Novel Inhibitors of HIV Protease Based on a Benzodiazepine Scaffold Structure-Aided Design of Novel Inhibitors of HIV Protease Based on a Benzodiazepine Scaffold (en)
skos:prefLabel	Structure-Aided Design of Novel Inhibitors of HIV Protease Based on a Benzodiazepine Scaffold Structure-Aided Design of Novel Inhibitors of HIV Protease Based on a Benzodiazepine Scaffold (en)
skos:notation	RIV/00216208:11310/12:10126790!RIV13-GA0-11310___
http://linked.open...avai/predkladatel	Přírodovědecká fakulta
http://linked.open...avai/riv/aktivita	I P S Z
http://linked.open...avai/riv/aktivity	I, P(GAP207/11/1798), P(GBP208/12/G016), S, Z(AV0Z40550506), Z(AV0Z50520514)
http://linked.open...iv/cisloPeriodika	22
http://linked.open...vai/riv/dodaniDat	2013
http://linked.open...aciTvurceVysledku	Veselý, Jan Císařová, Ivana Schimer, Jiří Konvalinka, Jan
http://linked.open.../riv/druhVysledku	J - Článek v odborném periodiku
http://linked.open...iv/duvernostUdaju	S - Úplné a pravdivé údaje nepodléhající ochraně podle zvláštních právních předpisů
http://linked.open...titaPredkladatele	Univerzita Karlova v Praze / Přírodovědecká fakulta
http://linked.open...dnocenehoVysledku	171908
http://linked.open...ai/riv/idVysledku	RIV/00216208:11310/12:10126790
http://linked.open...riv/jazykVysledku	eng - angličtina
http://linked.open.../riv/klicovaSlova	refinement; validation; binding; model; drug-resistance (en)
http://linked.open.../riv/klicoveSlovo	refinement model validation binding drug-resistance
http://linked.open...odStatuVydavatele	US - Spojené státy americké
http://linked.open...ontrolniKodProRIV	[B986E329E7A6]
http://linked.open...i/riv/nazevZdroje	Journal of Medicinal Chemistry
http://linked.open...in/vavai/riv/obor	CE
http://linked.open...ichTvurcuVysledku	4 (xsd:int)
http://linked.open...cetTvurcuVysledku	12 (xsd:int)
http://linked.open...vavai/riv/projekt	Controlling structure and function of biomolecules at the molecular scale: theory meets experiment HIV protease inhibitors: mechanism of action and resistance development
http://linked.open...UplatneniVysledku	2012
http://linked.open...v/svazekPeriodika	55
http://linked.open...iv/tvurceVysledku	Brynda, Jiří Cígler, Petr Císařová, Ivana Konvalinka, Jan Kožíšek, Milan Lepšík, Martin Veselý, Jan Řezáčová, Pavlína Schimer, Jiří Grantz Šašková, Klára Kraeusslich, Hans-Georg Oberwinkler, Heike
http://linked.open...ain/vavai/riv/wos	000311461500059
http://linked.open...n/vavai/riv/zamer	Regulace biologických procesů: Chemické modulátory vybraných systémů významných pro medicínu a zemědělství Molekulárně genetické a buněčné základy klíčových biologických procesů: genová exprese, onkogeneze, replikace virů, imunita a vývoj organismů
issn	0022-2623
number of pages	6 (xsd:int)
http://bibframe.org/vocab/doi	10.1021/jm301249q
http://localhost/t...ganizacniJednotka	11310
is http://linked.open...avai/riv/vysledek of	Structure-Aided Design of Novel Inhibitors of HIV Protease Based on a Benzodiazepine Scaffold

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