Pyridine coenzyme analogues. Synthesis and characterization of alpha- and beta-nicotinamide arabinoside adenine dinucleotides.
The synthesis and characterization of a new pyridine coenzyme analogue containing a nicotinamide arabinonucleotide moiety are reported. The redox potentials are -339 mV for beta-oxidized nicotinamide arabinoside adenine dinucleotide and -319 mV for alpha-oxidized nicotinamide adenine dinucleotide, and the lambda max is 346 and 338 nm for beta- and alpha-reduced nicotinamide arabinoside adenine dinucleotides (araNADH), respectively. Anomerization of the reduced analogues leads to a 5:1 ratio of alpha-araNADH to beta-araNADH at 90 degrees C. These results establish that the relative configuration of the 2'-hydroxyl to the base is the primary determinant for the configuration-dependent changes in lambda max, the redox potential of the pyridine nucleotides, and the preferred anomeric configuration of the reduced coenzymes. Comparison of the 1H and 31P NMR spectral data of the analogues with those for the ribo coenzymes is reported and the conformational analysis discussed. The coenzyme properties of the arabino analogues have been evaluated with yeast and horse liver alcohol dehydrogenases. Both the alpha- and beta-anomers are found to serve as coenzymes, and the stereochemistry of hydride transfer is identical for both anomers.
Kam
B L
BL
Department of Pharmaceutical Chemistry, University of California, San Francisco 94143.
Malver
O
O
Marschner
T M
TM
Oppenheimer
N J
NJ
D000426:Alcohol Dehydrogenase / Q000378:metabolism*; D000818:Animals; D006736:Horses; D007202:Indicators and Reagents; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D009243:NAD / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D013329:Structure-Activity Relationship
D007202:Indicators and Reagents; D009243:NAD; C053851:nicotinamide arabinoside adenine dinucleotide; D000426:Alcohol Dehydrogenase