INTERACTION OF AZA AND DEAZA ANALOGS OF ADENOSINE CYCLIC 3', 5'-PHOSPHATE WITH SOME ENZYMES OF ADENOSINE CYCLIC 3', 5'-PHOSPHATE METABOLISM - EVIDENCE THAT LONE PAIR ELECTRONS OF N-3 ARE INVOLVED IN BINDING OF ADENOSINE CYCLIC 3', 5'-PHOSPHATE TO TYPE-II ADENOSINE CYCLIC 3', 5'-PHOSPHATE-DEPENDENT PROTEIN-KINASEE
Five heterocyclic analogs of cyclic[c]AMP were examined for their ability to stimulate type II cyclic AMP-dependent kinases from bovine brain, bovine heart and rat liver; to serve as substrates for high Km (Km for cyclic AMP = 0.13-0.43 mM) cyclic nucleotide phosphodiesterases from bovine heart, rabbit kidney and rat liver and to inhibit the hydrolysis of cyclic AMP catalyzed by low Km (Km for cAMP = 0.32-1.5 .mu.M) cyclic nucleotide phosphodiesterases from bovine brain, bovine heart, dog heart, rabbit liver, rat brain and rat liver. The analogs all had a purine ring system which was modified by replacement of a ring C with N or vice versa to yield 2-aza-cAMP (7-amino-4-.beta.-D-ribofuranosylimidazo [4,5-d] -v-triazine cyclic 3'',5''-phosphate); 8-aza-cAMP (7-amino-3-.beta.-D-ribofuranosyl-v-triazolo-[4,5-d]-pyrimidine cyclic 3'',5''-phosphate); 1 deaza-cAMP (7-amino-3-.beta.-D-ribofuranosylimidazo [4,5-b]pyridine cyclic 3'',5''-phosphate); 3-deaza-cAMP (4-amino-1-.beta.-D-ribofuranosylimidazo[4,5-c]pyridine cyclic 3'',5''-phosphate) and 7-deaza-cAMP (7-amino-4-.beta.-D-ribofuranosylpyrrolo[2,3-d]pyrimidine cyclic 3'',5''-phosphate).