Structure-Aided Design of Novel Inhibitors of HIV Protease Based on a Benzodiazepine Scaffold
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F12%3A10126790" target="_blank" >RIV/00216208:11310/12:10126790 - isvavai.cz</a>
Alternative codes found
RIV/68378050:_____/12:00385940 RIV/61388963:_____/12:00385940
Result on the web
<a href="http://dx.doi.org/10.1021/jm301249q" target="_blank" >http://dx.doi.org/10.1021/jm301249q</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1021/jm301249q" target="_blank" >10.1021/jm301249q</a>
Alternative languages
Result language
angličtina
Original language name
Structure-Aided Design of Novel Inhibitors of HIV Protease Based on a Benzodiazepine Scaffold
Original language 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.
Czech name
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Czech description
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Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
CE - Biochemistry
OECD FORD branch
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Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2012
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of Medicinal Chemistry
ISSN
0022-2623
e-ISSN
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Volume of the periodical
55
Issue of the periodical within the volume
22
Country of publishing house
US - UNITED STATES
Number of pages
6
Pages from-to
10130-10135
UT code for WoS article
000311461500059
EID of the result in the Scopus database
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