HYDROLYSIS OF NUCLEOSIDE 5'-PHOSPHONATES AND PHOSPHATES BY PHOSPHATASES OF DIFFERENT ORIGIN AND HUMAN OR CALF SERA

The resistance of various 5'-phosphonates of 2'-deoxythymidine and its analogs modified at the 3' Position, which inhibit reproduction of th e human immunodeficiency virus (HIV), to the action of Escherichia col i alkaline phosphatase, calf intestinal phosphatase, and human placent al phosphatase was demonstrated. The cleavage rate of the phosphate gr oup of nucleotides modified at the ribose residue was independent of t he nature of the substituent at the ribose 3' atom. Cobra venom (Crota lus atrox) 5'-nucleotidase catalyzed the hydrolysis of some phosphonat e groups; the hydrolysis rate was dependent on the nature of the subst ituent at the phosphorus atom as well as on the character of sugar mod ification. The conversions of adenosine and its 5'-phosphonates and ph osphates during incubation with human umbilical and fetal calf serum w ere studied. Incubation of 2'-deoxyadenosine with human or calf serum resulted in its deamination to 2'-deoxyinosine followed by base cleava ge and formation of hypoxanthine. 2'-Deoxyadenosine 5'-phosphonates we re stable during incubation with human and calf serum under the same c onditions.