FLinT Center, Institut for Fysik, Kemi og Farmaci (IFKF), University of Southern Denmark, Campusvej 55, 5230 Odense, Denmark.
Chembiochem. 2013 Jan 21;14(2):217-23. doi: 10.1002/cbic.201200643. Epub 2012 Dec 18.
A new scenario for prebiotic formation of nucleic acid oligomers is presented. Peptide catalysis is applied to achieve condensation of activated RNA monomers into short RNA chains. As catalysts, L-dipeptides containing a histidine residue, primarily Ser-His, were used. Reactions were carried out in self-organised environment, a water-ice eutectic phase, with low concentrations of reactants. Incubation periods up to 30 days resulted in the formation of short oligomers of RNA. During the oligomerisation, an active intermediate (dipeptide-mononucleotide) is produced, which is the reactive species. Details of the mechanism and kinetics, which were elucidated with a set of control experiments, further establish that the imidazole side chain of a histidine at the carboxyl end of the dipeptide plays a crucial role in the catalysis. These results suggest that this oligomerisation catalysis occurs by a transamination mechanism. Because peptides are much more likely products of spontaneous condensation than nucleotide chains, their potential as catalysts for the formation of RNA is interesting from the origin-of-life perspective. Finally, the formation of the dipeptide-mononucleotide intermediate and its significance for catalysis might also be viewed as the tell-tale signs of a new example of organocatalysis.
提出了一种新的核酸低聚物前体形成的情景。采用肽催化实现激活的 RNA 单体缩合成短的 RNA 链。作为催化剂，使用含有组氨酸残基的 L-二肽，主要是 Ser-His。反应在自组织环境中进行，水-冰共晶相中反应物浓度低。孵育时间长达 30 天，导致 RNA 短寡聚物的形成。在寡聚化过程中，产生了一种活性中间体（二肽-单核苷酸），它是反应性物质。通过一组对照实验阐明的机制和动力学细节进一步表明，二肽羧基端组氨酸的咪唑侧链在催化中起着关键作用。这些结果表明，这种寡聚化催化是通过转氨基作用机制发生的。由于肽比核苷酸链更有可能是自发缩合的产物，因此从生命起源的角度来看，它们作为 RNA 形成的催化剂具有一定的潜力。最后，二肽-单核苷酸中间体的形成及其对催化的意义也可以被视为有机催化的一个新实例的明显标志。
