Design of purine nucleoside phosphorylase inhibitors
Stoeckler, J.D.; Ealick, S.E.; Bugg, C.E.; Parks, R.E.
Federation Proceedings 45(12): 2773-2778
1986
ISSN/ISBN: 0014-9446 PMID: 3095150 Document Number: 269799
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.