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  • Title: Design of purine nucleoside phosphorylase inhibitors.
    Author: Stoeckler JD, Ealick SE, Bugg CE, Parks RE.
    Journal: Fed Proc; 1986 Nov; 45(12):2773-8. PubMed ID: 3095150.
    Abstract:
    Purine nucleoside phosphorylase inhibitors hold promise as specific immunosuppressive, anti-T cell leukemic, and antiuricopoietic agents. The best inhibitors available that are biologically active have Ki values from 10(-6) to 10(-7) M and fall into two categories: noncleavable nucleosides preferably iodinated at the C-5' position and C-8-substituted guanine or acycloguanosines. More potent inhibition is shown by phosphorylated acyclonucleosides that function as multisubstrate analogs, but these compounds are excluded from cells. The X-ray analysis of the human erythrocytic enzyme is beginning to reveal the nature of the active site and to explain the structure-activity relationships that have been established with analog substrates and inhibitors.
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