Inhibition of purine nucleoside phosphorylase by N9- and N7-β-D-glucofuranuronosil purines and C8-substituted β-D-ribofuranosil purines

A. V. Ananiev, Y. Maurins, B. Paegle, M. Y. Lidaks, Zh. I. Akopyan

Institute of Experimental Biology, Armenian Academy of Sciences, Yerevan; Institute of Organic Synthesis, Latvian Academy of Sciences, Riga

Abstract: In an effort to develop more potent inhibitors of purine nucleoside phosphorylase (PNP, EC as immunosuppressive and anticancer chemotherapeutic agents, the affinity of the electrophoretically homogeneous enzyme from rabbit kidney for sixteen N9- and N7-β-D-glucofuranuronosides and for C8-substituted β-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.

Russian Journal of Bioorganic Chemistry 1991, 17 (6):855-856

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