Binding specificities of adenosine aminohydrolase from calf intestinal mucosa with dialdehydes derived from hexofuranosyladenine nucleosides

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Abstract
A series of nucleoside dialdehydes [potential anticancer chemotherapeutics] were prepared as powders after treatment of hexofuranosyladenine nucleosides with paraperiodic acid; periodate oxidation and purification of the products yielded dialdehydes derived from 9-(6-deoxy-.beta.-D-gulofuranosyl)adenine (1), 9-(6-deoxy-.beta.-L-gulofuranosyl)adenine (2), 9-(.alpha.-D-rhamnofuranosyl)adenine (3), 9-(.alpha.-L-rhamnofuranosyl)adenine (4), 9-(6-deoxy-.alpha.-L-talofuranosyl)adenine (5), 9-(5,6-dideoxy-.beta.-L-ribo-hex-5-enofuranosyl)adenine (6) and 9-(5,6-dideoxy-.beta.-D-ribo-hex-5-enofuranosyl)adenine (7). Nucleoside dialdehydes 1, 4 and 5 were weak substrates for adenosine aminohydrolase from calf intestinal mucosa. Dialdehydes 6 and 7 were not substrates for the enzyme but were rather strong competitive inhibitors, with Ki values of 50 and 7 .mu.M, respectively. Dialdehydes 2 and 3 did not bind to the enzyme at all. The dialdehydes did not exhibit time-dependent inhibition, suggesting that they did not form covalent bonds with the protein.