Molecular Pharmacology, Vol 5, 263-270, Copyright © 1969 by the American Society for Pharmacology and Experimental Therapeutics

The Effects of 6-Chloro-8-aza-9-cyclopentylpurine on Nucleic Acid and Protein Synthesis in Escherichia coli

I. In Vivo Studies

¹ Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510
² Department of Pharmacology, The University of Michigan Medical School, Ann Arbor, Michigan 48104

6-Chloro-8-aza-9-cyclopentylpurine, a purine deoxyribonucleoside analogue, inhibited the synthesis of DNA, RNA, and protein, as well as the induction of -galactosidase, in Escherichia coli B. Its effects were studied under conditions which allowed partial dissection of the inhibitions caused by this agent on the various macromolecular processes. E. coli B3, a thymidine-requiring mutant, and T2osr bacteriophage were employed for these purposes. The data indicate that the synthesis of DNA is more sensitive to 6-chloro-8-aza-9-cyclopentylpurine than is the formation of either RNA or protein. Blockade by this agent of the synthesis of RNA and protein appears to be independent of its effects on the processes involved in the formation of DNA. The induced synthesis of -galactosidase is considerably more sensitive to the inhibitory effects of 6-chloro-8-aza-9-cyclopentylpurine than is the formation of total cellular protein. The results support the concept that there are multiple sites of blockade by the purine deoxyribonucleoside analogue.

Note:
ACKNOWLEDGMENTS The authors wish to express their sincere thanks to Miss Bonnie Wachter and Miss Linda Galligher for excellent assistance, and to Dr. Barry Goz for his advice and help with the experiments employing bacteriophage.