Medical Research Council Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge Biomedical Campus, Cambridge CB2 0QH, UK.
Nat Chem. 2013 May;5(5):383-9. doi: 10.1038/nchem.1626. Epub 2013 Apr 14.
The recent synthesis of pyrimidine ribonucleoside-2',3'-cyclic phosphates under prebiotically plausible conditions has strengthened the case for the involvement of ribonucleic acid (RNA) at an early stage in the origin of life. However, a prebiotic conversion of these weakly activated monomers, and their purine counterparts, to the 3',5'-linked RNA polymers of extant biochemistry has been lacking (previous attempts led only to short oligomers with mixed linkages). Here we show that the 2'-hydroxyl group of oligoribonucleotide-3'-phosphates can be chemoselectively acetylated in water under prebiotically credible conditions, which allows rapid and efficient template-directed ligation. The 2'-O-acetyl group at the ligation junction of the product RNA strand can be removed under conditions that leave the internucleotide bonds intact. Remarkably, acetylation of mixed oligomers that possess either 2'- or 3'-terminal phosphates is selective for the 2'-hydroxyl group of the latter. This newly discovered chemistry thus suggests a prebiotic route from ribonucleoside-2',3'-cyclic phosphates to predominantly 3',5'-linked RNA via partially 2'-O-acetylated RNA.
在类似原始生命条件下，嘧啶核苷 2',3'-环磷酸酯的最近合成，强化了 RNA 在生命起源早期参与的观点。然而，这些弱活性单体及其嘌呤对应物到现存生物化学中 3',5'-连接的 RNA 聚合物的前生物转化一直缺乏（以前的尝试仅导致具有混合键的短寡聚物）。在这里，我们表明，寡核苷酸 3'-磷酸酯的 2'-羟基在类似原始生命条件下的水中可以进行化学选择性乙酰化，从而允许快速和有效的模板指导连接。产物 RNA 链连接连接处的 2'-O-乙酰基可以在保持核苷酸间键完整的条件下除去。值得注意的是，具有 2'-或 3'-末端磷酸酯的混合寡聚物的乙酰化对后者的 2'-羟基具有选择性。这种新发现的化学物质因此提供了一条从核苷 2',3'-环磷酸酯到主要为 3',5'-连接的 RNA 的前生物途径，通过部分 2'-O-乙酰化的 RNA。
