Some inhibitors of purine nucleoside phosphorylase

Pogosian L.H.1 , Nersesova L.S.1, Gazariants M.G.1, Mkrtchian Z.S.1, Akopian J.I.1

1. Institute of Molecular Biology of NAS RA, Laboratory of Molecular Enzymology
Section: Experimental/Clinical Study
DOI: 10.18097/PBMC20115705526      PubMed Id: 22629603
Year: 2011  Volume: 57  Issue: 5  Pages: 526-534
Purine nucleoside phosphorylase (PNP) catalyzes reversible phosphorolysis of purine deoxy- and ribonucleosides with formation (d)Rib-1-P and corresponding bases. PNP plays a leading role in the cell metabolism of nucleosides and nucleotides, as well as in maintaining the immune status of an organism. The major aim of the majority of studies on the PNP is the detection of highly effective inhibitors of this enzyme, derivatives of purine nucleosides used in medicine as immunosuppressors, which are essential for creating selective T-cell immunodeficiency in a human body for organ and tissue transplantation.The present work is devoted to the study of the effects of some synthetic derivatives of purine nucleosides on activity of highly purified PNP from rabbit spleen and also from human healthy and tumor tissues of lung and kidneys. Purine nucleoside analogues modified at various positions of both the heterocyclic base and carbohydrate residues have been investigated. Several compounds, including 8-mercapto-acyclovir, 8-bromo-9-(3,4-hydroxy-butyl)guanine, which demonstrated potent PNP inhibition, could be offered for subsequent study as immunosuppressors during organ and tissue transplantation.
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Keywords: purine nucleoside phosphorylase, activity, substrates, inhibitors, tumor tissues, medicinal preparations

Pogosian, L. H., Nersesova, L. S., Gazariants, M. G., Mkrtchian, Z. S., Akopian, J. I. (2011). Some inhibitors of purine nucleoside phosphorylase. Biomeditsinskaya Khimiya, 57(5), 526-534.
This paper is also available as the English translation: 10.1134/S1990750811010094
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