Kam B L, Malver O, Marschner T M, Oppenheimer N J
Department of Pharmaceutical Chemistry, University of California, San Francisco 94143.
Biochemistry. 1987 Jun 16;26(12):3453-61. doi: 10.1021/bi00386a031.
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.
报道了一种含烟酰胺阿拉伯核苷酸部分的新型吡啶辅酶类似物的合成与表征。β-氧化烟酰胺阿拉伯糖苷腺嘌呤二核苷酸的氧化还原电位为-339 mV，α-氧化烟酰胺腺嘌呤二核苷酸的氧化还原电位为-319 mV，β-还原和α-还原烟酰胺阿拉伯糖苷腺嘌呤二核苷酸（araNADH）的最大吸收波长分别为346和338 nm。还原类似物的异头化在90℃时导致α-araNADH与β-araNADH的比例为5:1。这些结果表明，2'-羟基与碱基的相对构型是最大吸收波长、吡啶核苷酸氧化还原电位以及还原辅酶的优选异头构型中构型依赖性变化的主要决定因素。报道了类似物与核糖辅酶的1H和31P NMR光谱数据的比较，并讨论了构象分析。用酵母和马肝醇脱氢酶评估了阿拉伯类似物的辅酶性质。发现α-和β-异头物均作为辅酶，并且两种异头物的氢化物转移立体化学相同。
