Strategy for Industrial Scale Production of Dideoxyinosine: Enzymatic Deamination of Dideoxyadenosine by Adenosine Deaminase

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Abstract
A procedure has been devised for the production of dideoxyinosine (ddI) in high yield and purity. The method employs adenosine deaminase to deaminate 2′,3′-dideoxyadenosine (ddA) to ddI. On the basis of systematic evaluation of various reaction conditions, a substrate concentration of 0.5 M ddA and an enzyme concentration of 5.6 units per ml were selected, and all buffers were eliminated. Under these conditions ddA was quantitatively converted to ddI within 4 hrs. Addition of 25% DMSO to the reaction facilitated the isolation of ddI as a result of the differential solubilities of the product and substrate, but did not affect the enzymatic reaction. An industrial scale reaction has been designed on the basis of the data presented.