Purine Nucleoside Phosphorylase

Measurement of Activity and Use of Inhibitors
  • Johanna D. Stoeckler
  • Robert E. ParksJr.

Abstract

It has long been appreciated that purine nucleoside phosphorylase (PNP; purine nucleoside: orthophosphate ribosyltransferase, EC 2.4.2.1) may play a role in cancer chemotherapy by catalyzing the degradation of potentially cytotoxic purine deoxynucleoside analogs, e.g., 2′-deoxy-6-thioguanosine. More recently, the identification of an immunodeficiency disorder associated with a deficiency in PNP (Giblett et al., 1975) has drawn attention to this enzyme as a possible target for the design of novel immunosuppressive agents. In contrast to the severe combined immunodeficiency disease seen with adenosine deaminase deficiency, where defects occur in both cellular and humoral immunity, patients with PNP deficiency lack cellular, but not humoral, immunity. Also, these individuals excrete the more soluble nucleosides of hypoxanthine and guanine rather than the relatively insoluble end product of purine metabolism, uric acid. Thus it has been proposed that a potent inhibitor of PNP might serve as a biochemical modifier in chemotherapy with purine nucleoside analogs, as a selective immunosuppressive agent, and perhaps in the treatment of secondary gout (Parks et al., 1981; Stoeckler et al., 1980a, 1982; Kazmers et al., 1981).

Keywords

HPLC Adenosine Charcoal Hepes Adenine 

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Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • Johanna D. Stoeckler
    • 1
  • Robert E. ParksJr.
    • 1
  1. 1.Section of Biochemical Pharmacology Division of Biology and MedicineBrown UniversityProvidenceUSA

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