2',5'-DIDEOXYADENOSINE 3'-POLYPHOSPHATES ARE POTENT INHIBITORS OF ADENYLYL CYCLASES

2',5'-Dideoxyadenosine 3'-di- and triphosphates were tested as inhibit ors of brain adenylyl cyclases. With an IC50 similar to 40 nM, 2',5'-d ideoxy-3'-ATP is the most potent nonprotein synthetic regulator of ade nylyl cyclases thus far described. Neither 2',5'-dideoxy-3'-ADP nor 2' ,5'-dideoxy-3'-ATP inhibited activity by competition with substrate, a nd the linear noncompetitive inhibition observed was consistent with i nteraction via a distinct domain. The availability of this ligand will permit the development of a variety of probes that will be extremely useful in investigating adenylyl cyclase structure and the role(s) tha t this class of compound may play in physiologically regulating cell f unction.