Design of purine nucleoside phosphorylase inhibitors.
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.
D006801:Humans; D007700:Kinetics; D010430:Pentosyltransferases / Q000037:antagonists & inhibitors*; D010766:Phosphorylation; D011487:Protein Conformation; D011683:Purine-Nucleoside Phosphorylase / Q000037:antagonists & inhibitors* / Q000172:deficiency; D013329:Structure-Activity Relationship; D014961:X-Ray Diffraction
D010430:Pentosyltransferases; D011683:Purine-Nucleoside Phosphorylase