Chemical and enzymic routes for the synthesis of a fluorinated analogue of NAD+ were investigated. 3-Trifluoroacetylpyridine was successfully synthesised chemically and glycosidically linked to 2,3,5-tri-O-benzoyl-D-ribose, but debenzoylation of this product to give the mononucleoside proved impossible. Enzymic synthesis of 3-trifluoroacetylpyridine adenine dinucleotide from 3-trifluoroacetylpyridine and NAD+ in the presence of NAD+ transglycosidase from pig brain was unsuccessful. However, the fluorinated analogue of NAD+ was prepared by the incubation of 3-trifluoroacetylpyridine, PRPP and ATP in the presence of nicotinamide phosphoribosyl transferase (Lactobacillus fructosus) and NAD+ pyrophosphorylase. 3-Trifluoroacetylpyridine adenine dinucleotide was found to behave as an inhibitor, but not as a substrate in a number of dehydrogenase systems.
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