Dialdehydes derived from adenine nucleosides as substrates and inhibitors of adenosine aminohydrolase

A series of nucleoside dialdehydes have been obtained as powders after treatment of various adenine nucleosides with paraperiodic acid. Thus, oxidation gave dialdehydes derived from adenosine (1), 9-alpha-D-mannopyranosyladenine (2), 9-(5-deoxy-alpha-D-arabinofuranosyl)adenine (3), 9-alpha-L-rhamnopyranosyladenine (4), 9-beta-L-fucopyranosyladenine (5), 9-beta-D-fucopyranosyladenine (6), 9-alpha-D-arabinopyranosyladenine (7), 9-beta-D-ribopyranosyladenine (8), and 9-(5-deoxy-beta-D-erythro-pent-4-enofuranosyl)adenine (9). Nucleoside dialdehydes 1-3 and 6-8 were weak substrates for adenosine aminohydrolase from calf intestinal mucosa. Dialdehyde 8 had the strongest affinity, but 1 had the highest Vmax. All of the dialdehydes except 5 were inhibitors of the enzyme. The best inhibitors were 9 (Ki = 4 microM) and 4 (ki = 28 microM), and neither were substrates. The inhibitors did not exhibit time-dependent inhibition and did not appear to form covalent bonds with the protein. The data strongly suggest that the active form of the dialdehydes is as the open-chain dihydrates. The alcohol obtained by reduction of 9 (compound 10) was the strongest inhibitor (Ki = 0.9 microM among the related alcohols and the nucleoside dialdehydes.