Immucillins as antibiotics for T-cell proliferation and malaria

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Abstract

The genetic deficiency of human PNP causes a specific immunodeficiency by inducing apoptosis in dividing T-cells. Powerful inhibitors of PNP have been designed from the experimental determination of the transition state structure of PNPs. The Immucillins are transition state analogue inhibitors with K d values as low as 7 pM. In the presence of deoxyguanosine the Immucillins kill activated human T-cells but not other cell types. The Immucillins are orally available and of low toxicity to mice. Immucillins also inhibit PNP from Plasmodium falciparum. Parasites cultured in human erythrocytes are killed by purine starvation in the presence of Immucillins and can be rescued by hypoxanthine.

Original languageEnglish (US)
Pages (from-to)1305-1311
Number of pages7
JournalNucleosides, Nucleotides and Nucleic Acids
Volume23
Issue number8-9
DOIs
StatePublished - Dec 23 2004

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Keywords

  • DADMe-Immucillin-H
  • Immucillin-H
  • Malaria
  • Purine nucleoside phosphorylase
  • Purine salvage Transition state
  • T-cell proliferation
  • Transition state analogues

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Genetics

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