2',5'-dideoxyadenosine 3'-polyphosphates are potent inhibitors of adenylyl cyclases

2',5'-Dideoxyadenosine 3'-di- and triphosphates were tested as inhibitors of brain adenylyl cyclases. With an IC50 similar to 40 nM, 2',5'-dideoxy-3'-ATP is the most potent nonprotein synthetic regulator of adenylyl cyclases thus far described. Neither 2',5'-dideoxy-3'-ADP nor 2',5'-dideoxy-3'-ATP inhibited activity by competition with substrate, and the linear noncompetitive inhibition observed was consistent with interaction 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) that this class of compound may play in physiologically regulating cell function.