[Inhibition of activity of purine nucleoside phosphorylase with N9- and N7-(beta-D-glucofuranuronosyl)purines and 8-substituted N9-(beta-D-ribofuranosyl)purines)].
In an effort to develop more potent inhibitors of purine nucleoside phosphorylase (PNP, EC 2.4.2.1) as immunosuppressive and anticancer chemotherapeutic agents, the affinity of the electrophoretically homogeneous enzyme from rabbit kidney for sixteen N9- and N7-beta-D-glucofuranuronosides and for C8-substituted beta-D-ribofuranosyl purines was determined. In all cases N7-substituted analogues of hypoxanthine and guanine were twice more active inhibitors of PNP than N9-substituted compounds. No effective inhibitors were found among the C8-substituted analogues, apparently due to the bulky C8-groups hindering rotation around the glycosidic bond and thus preventing optimal binding with the enzyme.
Anan'ev
A V
AV
Maurin'sh
Iu A
IuA
Paégle
R A
RA
Lidak
M Iu
MIu
Akopian
Zh I
ZhI
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis; D007166:Immunosuppressive Agents / Q000138:chemical synthesis; D007668:Kidney / Q000201:enzymology; D011684:Purine Nucleosides / Q000494:pharmacology*; D011683:Purine-Nucleoside Phosphorylase / Q000037:antagonists & inhibitors*; D011817:Rabbits; D012263:Ribonucleosides / Q000494:pharmacology*
D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D011684:Purine Nucleosides; D012263:Ribonucleosides; D011683:Purine-Nucleoside Phosphorylase
Ingibirovanie aktivnosti purinnukleozidfosforilazy N9- i N7-(beta-D-gliukofuranuronozil)puranami i 8-zameshchennymi N9-(beta-D-ribofuranozil)purinami.