Inhibition of terminal deoxynucleotidyl transferase by adenine dinucleotides. Unique inhibitory action of Ap5A.
Terminal deoxynucleotidyltransferase (TdT) exhibits strong sensitivity to ATP and its dinucleotide analogues, Ap2A, Ap3A, Ap4A, Ap5A and Ap6A. Similar to ATP, all of the dinucleotides appear to be competitive inhibitors of TdT catalysis with respect to substrate deoxynucleoside triphosphates and effectively block the UV-mediated substrate cross-linking to TdT. Among the various dinucleotides, Ap5A and Ap6A (diadenosine 5'-5' penta- and hexaphosphate, respectively) are significantly more effective than dinucleotides containing 2, 3 or 4 phosphate backbones. Furthermore, Ap5A is found to be the only dinucleotide which has reactivity at both substrate- and primer-binding domains in TdT.
D000227:Adenine Nucleotides / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D004253:DNA Nucleotidylexotransferase / Q000037:antagonists & inhibitors*; D004254:DNA Nucleotidyltransferases / Q000037:antagonists & inhibitors*; D015226:Dinucleoside Phosphates; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D013942:Thymine Nucleotides / Q000378:metabolism
D000227:Adenine Nucleotides; D015226:Dinucleoside Phosphates; D013942:Thymine Nucleotides; C012275:P(1),P(5)-di(adenosine-5'-)pentaphosphate; C020733:diadenosine tetraphosphate; D000255:Adenosine Triphosphate; D004254:DNA Nucleotidyltransferases; D004253:DNA Nucleotidylexotransferase; C024157:thymidine 5'-triphosphate