Systems Chemistry in the Prebiotic Synthesis of RNA

然而，在地球上生命的起源期间，有一个阶段，核酸RNA起到了信息存储和催化的双重作用。“RNA世界假说”得到了最近许多生物学工作的有力支持，但在我们最近由EPSRC资助的工作之前，关于RNA可能是如何在早期地球上产生的，几乎没有化学解释。引用《纽约时报》今年早些时候一篇关于我们工作的文章：20多年来，研究人员一直在研究这个问题。核糖核酸的每个组成单元都由一个化学碱基、一个称为核糖的糖分子和一个磷酸基团组成。化学家们很快发现了这些成分中每一种都是从天然化学物质中形成的看似合理的自然方法。但没有一种自然的方式让他们所有人都走到一起。两位主要研究人员杰拉尔德·乔伊斯和莱斯利·奥格尔在1999年写道，这种核苷酸在原始地球上的自发出现几乎是一个奇迹。其他人则如此绝望，以至于他们相信RNA之前一定有其他分子，于是开始寻找RNA之前的世界。现在，奇迹似乎已经被解释了。在《自然》杂志的文章中，萨瑟兰博士和他的同事马修·W·鲍纳和巴特丽斯·格兰德报告说，他们服用了其他人使用的相同的起始化学物质，但导致他们的反应顺序和组合与之前的实验不同。他们在研究了所有可能的起始化学品组合10年后，发现了他们的配方，这一配方远非直观。他们没有让起始的化学物质形成糖和碱，而是以不同的顺序将它们混合，在这种顺序中，这些化学物质自然形成了一种半糖半碱的化合物。当加入另一个半糖和半碱基时，就会产生一种称为核胞苷磷酸的RNA核苷酸。如果紫外线照射到混合物上，就会产生第二个核苷酸。到目前为止，情况还不错，但如果要制造RNA本身，还有相当多的工作要做，目前的提议是寻求资金来完成这项工作。特别是，我们想要：i)找到一种方法来激活嘌呤核苷酸--我们认为我们可以从嘧啶核苷酸合成的副产品中做到这一点)解决手性问题(某些分子以左手和右手形式存在，而rna是右手核苷酸的聚合物)-我们认为我们可以通过结晶化‘技巧’来实现这一点，然后是磷酸催化的反应ii)找到一条路线得到甘油醛，甘油醛是合成中的关键中间体，但不被认为是生物前原料分子。

It is though that during the origin of life on Earth there was a phase when the nucleic acid RNA served the dual roles of information storage and catalysis. The 'RNA world hypothesis' is strongly supported by much recent biological work, but until our recent EPSRC funded work, there had been little by way of chemical explanation as to how RNA might have been generated prebiotically on the early Earth. To quote from a New York Times article written about our work earlier this year: 'For more than 20 years researchers have been working on this problem. The building blocks of RNA, known as nucleotides, each consist of a chemical base, a sugar molecule called ribose and a phosphate group. Chemists quickly found plausible natural ways for each of these constituents to form from natural chemicals. But there was no natural way for them all to join together. The spontaneous appearance of such nucleotides on the primitive earth would have been a near miracle, two leading researchers, Gerald Joyce and Leslie Orgel, wrote in 1999. Others were so despairing that they believed some other molecule must have preceded RNA and started looking for a pre-RNA world.The miracle seems now to have been explained. In the article in Nature, Dr. Sutherland and his colleagues Matthew W. Powner and Batrice Gerland report that they have taken the same starting chemicals used by others but have caused them to react in a different order and in different combinations than in previous experiments. they discovered their recipe, which is far from intuitive, after 10 years of working through every possible combination of starting chemicals. Instead of making the starting chemicals form a sugar and a base, they mixed them in a different order, in which the chemicals naturally formed a compound that is half-sugar and half-base. When another half-sugar and half-base are added, the RNA nucleotide called ribocytidine phosphate emerges. A second nucleotide is created if ultraviolet light is shined on the mixture.'So far so good, but quite a bit remains to be done if RNA itself is to be made, and the current proposal seeks funds to finish the job. In particular, we want to:i) find a route to activated purine nucleotides - we think we can do this from a by-product of the pyrimidine nucleotide synthesisii) sort out the chirality issue (certain molecules exist in left and right handed forms, and RNA is a polymer of right handed nucleotides) - we think we can do this using a crystallisation 'trick' followed by a phosphate-catalysed reactioniii) find a route to glyceraldehyde which is a key intermediate in the synthesis, but which is not considered to have been a prebiotic feedstock moleculeiv) optimise conditions for stringing the activated nucleotides together to generate RNA