Enzymic Synthesis and Biochemical Activity of Various Indazole Adenine Dinucleotides

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Abstract
Each of 5- or 6-amino-, acetamido-, hydroxy-, methoxy-, and chloroindazoles (including an unsubstituted one) and β NAD were subjected to an NADase-catalyzed base-exchange reaction to produce a corresponding title compound with a 41–76% yield. A difficulty, due to the poor solubility in water of indazole bases, was overcome by the addition of DMSO (∼20%) without a remarkable decrease in NADase activity. In most cases, the obtained dinucleotides were ascertained to be N2-ribosylated compounds. From 5- and 6-aminoindazoles, however, N1-ribosylated dinucleotide was also obtained as a minor product. In some of the N2-ribosylated dinucleotides, an unusual tautomerism was suggested to occur on the benzene ring of an indazole moiety. Finally, the synthesized title compounds were examined for inhibition activity against NAD-linked inosine monophosphate dehydrogenase. Four compounds among them were markedly effective at a 10−3 M concentration.
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