Stereoelectronic Factors in the Binding of Substrate Analogues and Inhibitors to Purine Nucleoside Phosphorylase Isolated from Human Erythrocytes

Frank Jordan, Annie Wu

Research output: Contribution to journalArticlepeer-review

20 Scopus citations

Abstract

Several aspects of the stereoelectronic requirements of substrates of human erythrocytic purine nucleoside phosphorylase (E.C. 2.4.2.1) were elucidated providing the following information: (a) the N1 position cannot have a nonhydrogen substituent; (b) the 5'-OH group must be present for catalytic activity to be exhibited but is not an essential functional group for inhibitory action to be observed; (c) on the C8 position groups larger than -NH2 or -Br cannot be accommodated; (d) the syn-glycosyl conformation (i.e., 8-bromoguanosine) is acceptable but may not be an absolute requirement for phosphorolysis; (e) among nucleic base inhibitors methylation at N3, N7, or N9 vastly decreases the inhibitory properties as does a nitrogen in lieu of C-H in the 8 position. The results clearly indicate that this enzyme differs in its stereoelectronic requirements from the Escherichia coli enzyme.

Original languageEnglish (US)
Pages (from-to)877-882
Number of pages6
JournalJournal of medicinal chemistry
Volume21
Issue number9
DOIs
StatePublished - 1978

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery

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