Molecular Pharmacology, Vol 6, 468-473, Copyright © 1970 by the American Society for Pharmacology and Experimental Therapeutics

Effects of 6-N-Allyladenosine on Bacterial and Mammalian Cells

¹ Kettering-Meyer Laboratory, Southern Research Institute, Birmingham, Alabama 35205

The adenosine analogue 6-N-allyladenosine is toxic to Escherichia coli and to mammalian tumor cells in culture. In the presence of 6-N-allyladenosine, E. coli cells excrete xanthosine into the medium; the inhibition of growth of the bacteria caused by this agent is reversed by addition of guanine. Consistent with these observations is the potent inhibition of bacterial GMP synthetase [xanthosine 5'-phosphate:ammonia ligase (AMP), EC 6.3.4.1] by 6-N-allyladenosine.

The toxicity of 6-N-allyladenosine toward mammalian cells is different from that toward bacteria, for it is dependent upon phosphorylation of the analogue by adenosine kinase. Mutants which lack this emzyme are resistant to 6-N-allyladenosine. The mammalian GMP synthetase [xanthosine 5'-phosphate:L-glutamine amidoligase (AMP), EC 6.3.5.2] is not strongly inhibited by 6-N-allyladenosine, but in intact cells the analogue, presumably present as the nucleotide, is a potent inhibitor of an early step in the purine-biosynthetic pathway. However, inability to reverse the toxicity of 6-N-allyladenosine by 4-amino-5-imidazolecarboxamide or hypoxanthine implies that such an effect is not solely responsible for growth inhibition.

Note:
ACKNOWLEDGMENTS We are grateful to Miss D. Adamson and Mrs. M. H. Vail for provision of cell cultures and for evaluating toxicities toward the mammalian cell lines. Mrs. P. W. Allan performed the test for pseudo-feedback inhibition, and Mr. T. C. Herren assayed samples for radioactivity.