N-Phosphonocarbonylpyrrolidine Derivatives of Guanine: A New Class of Bi-Substrate Inhibitors of Human Purine Nucleoside Phosphorylase
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F12%3A11519" target="_blank" >RIV/00216208:11110/12:11519 - isvavai.cz</a>
Alternative codes found
RIV/61388963:_____/12:00379118 RIV/00064165:_____/12:11519
Result on the web
<a href="http://dx.doi.org/10.1021/jm201409u" target="_blank" >http://dx.doi.org/10.1021/jm201409u</a>
DOI - Digital Object Identifier
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Alternative languages
Result language
angličtina
Original language name
N-Phosphonocarbonylpyrrolidine Derivatives of Guanine: A New Class of Bi-Substrate Inhibitors of Human Purine Nucleoside Phosphorylase
Original language description
A complete series of pyrrolidine nucleotides, (3R)- and (3S)-3-(guanin-9-yl)pyrrolidin-1-N-ylcarbonylphosphonic acids and (3S,4R)-, (3R,4S)-, (3S,4S)-, and (3R,4R)-4-(guanin-9-yl)-3-hydroxypyrrolidin-l-N-ylcarbonylphosphonic acids, were synthesized and evaluated as potential inhibitors of purine nucleoside phosphorylase (PNP) isolated from peripheral blood mononuclear cells (PBMCs) and cell lines of myeloid and lymphoid origin. Two compounds, (S)-3-(guanin-9-yl)pyrrolidin-1-N-ylcarbonylphosphonic acid (2a) and (3S,4R)-4-(guanin-9-yl)-3-hydroxypyrrolidin-1-N-ylcarbonylphosphonic acid (6a), were recognized as nanomolar competitive inhibitors of PNP isolated from cell lines with K-i values within the ranges of 16-100 and 10-24 nM, respectively. The low K-MESG(i) and K-Pi(i) values of both compounds for PNP isolated from PBMCs suggest that these compounds could be bisubstrate inhibitors that occupy both the phosphate and nucleoside binding sites of the enzyme.
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
CB - Analytical chemistry, separation
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
Z - Vyzkumny zamer (s odkazem do CEZ)
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
4
Country of publishing house
US - UNITED STATES
Number of pages
10
Pages from-to
1612-1621
UT code for WoS article
000301156000016
EID of the result in the Scopus database
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