Enantiometric cross-inhibition in the synthesis of oligonucleotides on a nonchiral template
Enantiometric cross-inhibition in the synthesis of oligonucleotides on a nonchiral template
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DOI：
10.1021/ja963563c
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发表时间：
1997-02-12
影响因子：
15
通讯作者：
Orgel, LE
中科院分区：
文献类型：
--
作者：
Schmidt, JG;Nielsen, PE;Orgel, LE
手性单体的益生元合成总是产生外消旋混合物。然而，生命系统在其生物聚合物中利用L-氨基酸和D-核苷酸。因此，在自催化过程中通过选择和放大产生的光学不对称性是许多生命起源理论中的一个重要因素。1-3模板定向合成中的多核苷酸复制是前“RNA世界”中这种扩增步骤的明显候选者。[4，5]对这一建议的一个严重的反对意见是观察到RNA的模板定向合成的效率受到对映体交联的限制。6肽核酸（PNA），7-9酰胺连接的RNA的非手性类似物，已被“复制”到RNA 10中，并作为信息复制系统构成手性多核苷酸的替代品。在这里，我们使用PNA作为模型的一个假设的，非手性前体的RNA在实验中重新检查对映体交叉抑制。以L-吡喃核糖（Sigma）为起始原料，采用成熟的合成方法11 -15合成了L-鸟苷5′-单磷酸（L-5 ′-GMP），产率18%。L-5′-GMP的所有分析数据与天然D-对映体的分析数据相同。L-5′-GMP转化为L-鸟苷5′-磷酸-2-甲基咪唑（L-2-MeImpG）（图1A），产率为95%。16选择我们的模板导向反应中的所有反应条件以便于与先前的反应条件进行比较。
Prebiotic syntheses of chiral monomers always yield racemic mixtures. Living systems, however, utilize L-amino acids and D-nucleotides in their biopolymers. The generation of optical asymmetry by selection and amplification in an autocatalytic process is, therefore, an important element in many theories of the origin of life. 1-3 Replication of polynucleotides in templatedirected syntheses is an obvious candidate for such an amplification step in a pre-“RNA world”. 4, 5 A serious objection to this suggestion is the observation that the efficiency of templatedirected syntheses of RNA is limited by enantiomeric crossinhibition. 6 Peptide nucleic acids (PNAs), 7-9 amide-linked, nonchiral analogues of RNA, have been “copied” into RNA10 and constitute an alternative to chiral polynucleotides as an informational replicating system. Here, we use PNA as model for a hypothetical, nonchiral precursor of RNA in experiments re-examining enantiomeric cross-inhibition. We find that enantiomeric cross-inhibition is as serious in the polymerization of nucleotides on a PNA template as it is on a conventional RNA or DNA template.L-Guanosine 5′-monophosphate (L-5′-GMP) was synthesized starting from L-ribopyranose (Sigma) following well-established procedures11-15 and gave L-5′-GMP in 18% yield. All analytical data for L-5′-GMP were identical to those for the natural D-enantiomer. L-5′-GMP was converted to L-guanosine 5′-phosphoro-2-methylimidazolide (L-2-MeImpG)(Figure 1A) in 95% yield. 16 All reaction conditions in our template-directed reactions were chosen to facilitate comparison with previously