Department of Chemistry, University College London, London, UK.
Nat Chem. 2022 Jul;14(7):766-774. doi: 10.1038/s41557-022-00982-5. Epub 2022 Jul 1.
Nucleosides are essential to the emergence of life, and so their synthesis is a key challenge for prebiotic chemistry. Although amino-nucleosides have enhanced reactivity in water compared with ribonucleosides, they are assumed to be prebiotically irrelevant due to perceived difficulties with their selective formation. Here we demonstrate that 3'-amino-TNA nucleosides (TNA, threose nucleic acid) are formed diastereoselectively and regiospecifically from prebiotic feedstocks in four high-yielding steps. Phosphate provides an unexpected resolution, leading to spontaneous purification of the genetically relevant threo-isomer. Furthermore, 3'-amino-TNA nucleosides are shown to be phosphorylated directly in water, under mild conditions with cyclic trimetaphosphate, forming a nucleoside triphosphate (NTP) in a manner not feasible for canonical nucleosides. Our results suggest 3'-amino-TNA nucleosides may have been present on the early Earth, and the ease with which these NTPs form, alongside the inherent selectivity for the Watson-Crick base-pairing threo-monomer, warrants further study of the role they could play during the emergence of life.
核苷是生命出现的必要条件，因此它们的合成是前生物化学的一个关键挑战。尽管氨基核苷在水中的反应性比核糖核苷强，但由于认为它们的选择性形成存在困难，因此被认为与前生物无关。在这里，我们证明 3'-氨基-TNA 核苷（TNA， threose nucleic acid）可以从前生物原料中以高产率的四个步骤选择性和区域特异性地形成。磷酸盐提供了一个意想不到的分辨率，导致遗传相关的 threo-异构体自发纯化。此外，在温和条件下用环三磷酸，在水中可以直接对 3'-氨基-TNA 核苷进行磷酸化，以对于典型核苷不可行的方式形成核苷三磷酸（NTP）。我们的结果表明，3'-氨基-TNA 核苷可能存在于早期地球上，并且这些 NTP 形成的容易程度以及对 Watson-Crick 碱基配对 threo-单体的固有选择性，值得进一步研究它们在生命出现过程中可能扮演的角色。
