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Biochemical Effects of Formycin, an Adenosine Analog¹

University of Alberta Cancer Research Unit (McEachern Laboratory), and Department of Biochemistry, Edmonton, Alberta, Canada

The effects of formycin (7-amino-3-(ß-D-ribofuranosyl) pyrazolo-(4,3-d)-pyrimidine), an adenosine analog, on purine metabolism in Ehrlich ascites tumor cells were studied. Purine biosynthesis de novo was blocked by formycin through inhibition of phosphoribosylpyrophosphate synthesis, and this did not occur in cells which did not phosphorylate formycin. This analog had no significant effect on adenine conversion to adenine and guanine nucleotides, but did inhibit the synthesis of these nucleotides from hypoxanthine and guanine. The incorporation of purines into nucleic acids was inhibited slightly. Formycin did not inhibit the phosphorolysis of guanosine or inosine, but did inhibit the incorporation of lysine and methionine into protein. Formycin 5'-phosphate inhibited adenine phosphoribosyltransferase but did not inhibit purine nucleoside kinase.

¹ Supported by the Medical Research Council and National Cancer Institute of Canada.

² Present address: Institute of Microbial Chemistry, Kamiosaki, Shinagawa-Ku, Tokyo, Japan.

Received 7/21/66. Accepted 12/ 1/66.

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