Peripheral but crucial: A hydrophobic pocket (Tyr(706), Leu(337), and Met(336)) for potent and selective inhibition of neuronal nitric oxide synthase
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F10%3A7217" target="_blank" >RIV/00216208:11110/10:7217 - isvavai.cz</a>
Alternative codes found
RIV/00064165:_____/10:7217
Result on the web
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DOI - Digital Object Identifier
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Alternative languages
Result language
angličtina
Original language name
Peripheral but crucial: A hydrophobic pocket (Tyr(706), Leu(337), and Met(336)) for potent and selective inhibition of neuronal nitric oxide synthase
Original language description
Selective inhibition of the neuronal isoform of nitric oxide synthase (nNOS) over endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) has become a promising strategy for the discovery of new therapeutic agents for neurodegenerative diseases. However, because of the high sequence homology of different isozymes in the substrate binding pocket, developing inhibitors with both potency and excellent isoform selectivity remains a challenging problem. Herein, we report the evaluation of a recently discovered peripheral hydrophobic pocket (Tyr(706), Leu(337), and Met(336)) that opens up upon inhibitor binding and its potential in designing potent and selective nNOS inhibitors using three compounds, 2a, 2b, and 3. Crystal structure results show that inhibitors 2a and 3 adopted the same binding mode as lead compound 1.
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
<a href="/en/project/1M0520" target="_blank" >1M0520: Center for Applied Genomics</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>Z - Vyzkumny zamer (s odkazem do CEZ)
Others
Publication year
2010
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Bioorganic & medicinal chemistry letters
ISSN
0960-894X
e-ISSN
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Volume of the periodical
20
Issue of the periodical within the volume
21
Country of publishing house
GB - UNITED KINGDOM
Number of pages
4
Pages from-to
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UT code for WoS article
000282677900022
EID of the result in the Scopus database
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