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首页> 外文期刊>Catalysis science & technology >Bio-catalytic synthesis of unnatural nucleosides possessing a large functional group such as a fluorescent molecule by purine nucleoside phosphorylase
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Bio-catalytic synthesis of unnatural nucleosides possessing a large functional group such as a fluorescent molecule by purine nucleoside phosphorylase

机译：Bio-catalytic不自然的核苷的合成拥有一个大型的官能团,如荧光分子通过嘌呤核苷磷酸化酶

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摘要

Unnatural nucleosides are attracting interest as potential diagnostic tools, medicines, and functional molecules. However, it is difficult to couple unnatural nucleobases to the 1 '-position of ribose in high yield and with beta-regioselectivity. Purine nucleoside phosphorylase (PNP, EC2.4.2.1) is a metabolic enzyme that catalyses the conversion of inosine to ribose-1 alpha-phosphate and free hypoxanthine in phosphate buffer with 100% alpha-selectivity. We explored whether PNP can be used to synthesize unnatural nucleosides. PNP catalysed the reaction of thymidine as a ribose donor with purine to produce 2 '-deoxynebularine (3, beta form) in high conversion (80%). It also catalysed the phosphorolysis of thymidine and introduced a pyrimidine base with a halogen atom substituted at the 5-position into the 1 '-position of ribose in moderate yield (52-73%), suggesting that it exhibits loose selectivity. For a bulky purine substrate [e.g., 6-(N,N-di-propylamino)], the yield was lower, but addition of a polar solvent such as dimethyl sulfoxide (DMSO) increased the yield to 74%. PNP also catalysed the reaction between thymidine and uracil possessing a large functional fluorescent group, 5-(coumarin-7-oxyhex-5-yn) uracil (C4U). Conversion to 2 '-deoxy-[5-(coumarin-7-oxyhex-5-yn)] uridine (dRC4U) was drastically enhanced by DMSO addition. Docking simulations between dRC4U and E. coli PNP (PDB ; 3UT6) showed the uracil moiety in the active-site pocket of PNP with the fluorescent moiety at the entrance of the pocket. Thus, the bulky fluorescent moiety has little influence on the coupling reaction. In summary, we have developed an efficient method for producing unnatural nucleosides, including purine derivatives and modified uracil, using PNP.
机译：不自然的核苷是吸引的兴趣潜在的诊断工具,药物,和功能分子。一些不自然的碱基1 ' -安置在高收益和核糖beta-regioselectivity。EC2.4.2.1磷酸化酶(PNP)是一个代谢酶,催化作用肌苷的转换对ribose-1 alpha-phosphate和自由次黄嘌呤在磷酸缓冲alpha-selectivity为100%。我们探讨了PNP型是否可以用来合成不自然的核苷。胸苷的捐助与嘌呤核糖生产2》-deoxynebularine(3β形式)高转化率(80%)。磷酸解胸苷和介绍了卤素原子取代嘧啶基地5-position到1的核糖-安置在温和的收益率(52 - 73%),这表明它展品宽松的选择性。底物(例如,6 - (N, N-di-propylamino)],产量较低,但添加一个极性溶剂如二甲亚砜(DMSO)增加了收益率74%。胸苷和尿嘧啶之间拥有一个大功能荧光集团(5 - coumarin-7-oxyhex-5-yn uracil C4U)。转换到2脱氧- 5 - (coumarin-7-oxyhex-5-yn)尿苷(dRC4U)被DMSO大大增强加法。大肠杆菌PNP型(PDB;在活性位点口袋PNP型的荧光一半入口处的口袋里。因此,笨重的荧光一部分几乎没有影响的耦合反应。我们已经开发出一种有效的方法产生不自然的核苷,包括嘌呤尿嘧啶衍生品和修改,使用PNP型。

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