Conformationally constrained nucleoside phosphonic acids - potent inhibitors of human mitochondrial and cytosolic 5'(3')-nucleotidases

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F14%3A00435239" target="_blank" >RIV/61388963:_____/14:00435239 - isvavai.cz</a>

Alternative codes found

RIV/68378050:_____/14:00435239 RIV/60461373:22330/14:43897213

Result on the web

<a href="http://dx.doi.org/10.1039/c4ob01332h" target="_blank" >http://dx.doi.org/10.1039/c4ob01332h</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/c4ob01332h" target="_blank" >10.1039/c4ob01332h</a>

Result language

angličtina

Original language name

Conformationally constrained nucleoside phosphonic acids - potent inhibitors of human mitochondrial and cytosolic 5'(3')-nucleotidases

Original language description

This work describes novel in vitro inhibitors of human mitochondrial (mdN) and cytosolic (cdN) 5'(3')-deoxynucleotidases. We designed a series of derivatives of the lead compound (S)-1-[2-deoxy-3,5-O-(phosphonobenzylidene)-beta-D-threo-pentofuranosyl] thymine bearing various substituents in the para position of the benzylidene moiety. Detailed kinetic study revealed that certain para substituents increase the inhibitory potency (iodo derivative; K-i(mdN) = 2.71 mu M) and some induce a shift in selectivity toward cdN (carboxy derivative, K-i(cdN) = 11.60 mu M; iodoxy derivative, K-i(cdN) = 6.60 mu M). Crystal structures of mdN in complex with three of these compounds revealed that various para substituents lead to two alternative inhibitor binding modeswithin the enzyme active site. Two binding modes were also identified for cdN complexes by heteronuclear NMR spectroscopy.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

CC - Organic chemistry

OECD FORD branch

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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>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2014

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Organic & Biomolecular Chemistry

ISSN

1477-0520

e-ISSN

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Volume of the periodical

12

Issue of the periodical within the volume

40

Country of publishing house

GB - UNITED KINGDOM

Number of pages

12

Pages from-to

7971-7982

UT code for WoS article

000342992400014

EID of the result in the Scopus database

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