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 ∼40 nM, 2′,5′-dideoxy-3′-ATP is the most potent non-protein 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. 2′,5′-Dideoxyadenosine 3′-di- and triphosphates were tested as inhibitors of brain adenylyl cyclases. With an IC50 ∼40 nM, 2′,5′-dideoxy-3′-ATP is the most potent non-protein 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.