Bis(isopropylidene adenosine)—A novel base-stacked dinucleoside with two deamination sites for adenosine deaminase

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Two adenosine molecules are connected via their ribose moieties by transacetalation with 2,2,5,5-tetraethoxyhexane, yielding diastereoisomeric bis(isopropylidene adenosine) compounds with S,S- ( 1a) or R,S-configurated ( 1b) acetal carbons. The S,S isomer shows high hypochromicity and a pronounced positive Cotton effect, which implies strong stacking interactions. The stacking of 1b is less pronounced. Both isomers are substrates for mammalian adenosine deaminase (EC 3.5.4.4.). Whereas compound 1a is slowly deaminated due to steric hindrance and stacking interactions, the diastereoisomer 1b is a much better substrate for the enzyme. Because of the difference in configuration in 1b the adenosine moieties are processed stepwise. Moreover, isomer 1b is a strong competitive inhibitor for the deamination of adenosine by the enzyme.