POTENT INHIBITION OF SPECIFIC DIADENOSINE POLYPHOSPHATE HYDROLASES BYSURAMIN

The cytosolic enzymes asymmetrical diadenosine tetraphosphate hydrolas e (EC 3.6.1.17, Ap(4)Aase) and diadenosine triphosphate hydrolase (EC 3.6.1.29, Ap(3)Aase) are inhibited competitively by suramin. Ap(4)Aase and Ap(3)Aase were assayed in cytosolic rat brain extracts using fluo rogenic analogues of the respective substates diadenosine tetraphospha te (Ap(4)A) and diadenosine triphosphate (Ap(3)A). K-i values for sura min as inhibitor of Ap(4)Aase and Ap(3)Aase were 5X10(-6) NI and 3x10( -7) M, respectively. Results indicate that suramin or suramin-like der ivatives may be useful tools to investigate diadenosine polyphosphate cleaving enzymes and that the intracellular diadenosine polyphosphate metabolism may be a pharmacological target of suramin with biological and clinical implications. (C) 1998 Federation of European Biochemical Societies.