Adenosine analog metabolism in Giardia lamblia. Implications for chemotherapy.

摘要: Certain adenosine analogs can inhibit the growth of Giardia lamblia. This biological action correlates with ability organism to phosphorylate nucleoside directly nucleotide. Four these, 8-azaadenosine, 1-deazaadenosine, 7-deazaadenosine, and 9-deazaadenosine, were very effective. The respective bases first three ineffective. base 9-deazaadenosine was not tested as this C-nucleoside is non-cleavable. Metabolic studies using radioactive 7- showed that these compounds phosphorylated by organism. Enzymatic assay confirmed presence phosphotransferase activity; no kinase activity found. Preliminary characterization suggests it has different substrate phosphate donor specificities than mammalian enzyme and, therefore, may be a potential site for chemotherapeutic attack.