Molecular Pharmacology, Vol 6, 24-30, Copyright © 1970 by the American Society for Pharmacology and Experimental Therapeutics

Analogues of Adenosine 3',5'-Cyclic Phosphate as Activators of Phosphorylase b Kinase and as Substrates for Cyclic 3',5'-Nucleotide Phosphodiesterase

¹ Department of Pharmacology, The University of British Columbia, Vancouver, 8, Canada

The ability of several analogues of adenosine cyclic 3',5'-phosphate to activate phosphorylase b kinase was investigated. Tubercidin 3',5'-cyclic phosphate was slightly more active than cyclic 3',5'AMP. Compounds that involve structural alteration of the phosphate moiety, such as adenosine 3',5'-cyclic phosphorothioate and two isomeric cyclic phosphonate compounds, were either extremely weak activators or inactive. Adenine 9--D-xylofuranosyl 3',5'-cyclic phosphate and N⁶, 2'-O-dibutyryl cyclic 3',5'-AMP, structures which involve modification of the sugar moiety, were also relatively inactive. The studies point to a remarkable specificity, especially with regard to the intactness of the phosphate moiety.

Of the compounds tested, only cyclic 3',5'-AMP and tubercidin 3',5'-cyclic phosphate were effective substrates for cyclic 3',5'-nucleotide phosphodiesterase. A marked requirement for the unmodified phosphate group is apparent for interaction with this enzyme, whereas there is less specificity with regard to the base moiety.

Note:
ACKNOWLEDGMENTS We wish to thank the various individuials named in the text for providing samples of the compounds tested. We are grateful to Drs. H. P. Bär and J. G. Moffatt for several helpful discussions, and to Dr. F. Eckstein for providing us information on adenosine 3',5'-cyclic phosphorothioate.