Prebiotically plausible oligoribonucleotide ligation facilitated by chemoselective acetylation.
Prebiotically plausible oligoribonucleotide ligation facilitated by chemoselective acetylation.
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最近，嘧啶核苷-2 ′，3 ′-环磷酸在前生物学上合理的条件下的合成加强了RNA参与生命起源早期阶段的情况。然而，这些弱活化单体及其嘌呤对应物向现存生物化学的3′，5 ′-连接的RNA聚合物的益生元转化一直缺乏-以前的尝试仅导致具有混合键的短寡聚体。在这里，我们表明寡核糖核苷酸-3 '-磷酸的2'-羟基可以在生物学上可靠的条件下在水中化学选择性乙酰化，从而实现快速有效的模板定向连接。在保持核苷酸间键完整的条件下，可以去除产物RNA链连接点处的2′-O-乙酰基。值得注意的是，具有2′-或3′-末端磷酸酯的混合低聚物的乙酰化对后者的2′-羟基具有选择性。因此，这种新发现的化学反应表明了从核糖核苷-2 ′，3 ′-环磷酸到主要是3′，5 ′-连接的RNA通过部分2′-O-乙酰化-RNA的益生元途径。
The recent synthesis of pyrimidine ribonucleoside-2′,3′-cyclic phosphates under prebiotically plausible conditions has strengthened the case for the involvement of 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 leading 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, allowing 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 possessing 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.