Kanavarioti A
Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA 95064, USA.
J Mol Evol. 1998 Jun;46(6):622-32. doi: 10.1007/pl00006342.
Phosphoimidazolide-activated ribomononucleotides (*pN; see Scheme I) are useful substrates for the nonenzymatic synthesis of oligonucleotides. In the presence of metal ions dilute neutral aqueous solutions of *pN (0.01 M) typically yield only small amounts of dimers and traces of oligomers; most of *pN hydrolyzes to yield nucleoside 5'-monophosphate (5'NMP). An earlier investigation of *pN reactions in highly concentrated aqueous solutions (up to 1.4 M) showed, as expected, that the percentage yield of the condensation products increases and the yield of the hydrolysis product correspondingly decreases with *pN concentration (Kanavarioti 1997). Here we report product distributions in reactions with one, two, or three reactive components at the same total nucleotide concentration. *pN used as substrates were the nucleoside 5'-phosphate 2-methylimidazolides, 2-MeImpN, with N = cytidine (C), uridine (U), or guanosine (G). Reactions were conducted as self-condensations, i. e., one nucleotide only, with two components in the three binary U,C, U,G, and C,G mixtures, and with three components in the ternary U,C, G mixture. The products are 5'NMP, 5',5'-pyrophosphate-, 2',5'-, 3', 5'-linked dimers, cyclic dimers, and a small percentage of longer oligomers. The surprising finding was that, under identical conditions, including the same total monomer concentration, the product distribution differs substantially from one reaction to another, most likely due to changing intermolecular interactions depending on the constituents. Even more unexpected was the observed trend according to which reactions of the U,C,G mixture produce the highest yield of internucleotide-linked dimers, whereas the self-condensations produce the least and the reactions with the binary mixtures produce yields that fall in between. What is remarkable is that the approximately two-fold increase in the percentage yield of internucleotide-linked dimers is not due to a concentration effect or a catalyst, but to the increased complexity of the system from a single to two and three components. These observations, perhaps, provide an example of how increased complexity in relatively simple chemical systems leads to organization of the material and consequently to chemical evolution. A possible link between prebiotic chemistry and the postulated RNA world is discussed.
磷酰咪唑活化的核糖核苷酸（pN；见方案I）是寡核苷酸非酶促合成的有用底物。在金属离子存在下，pN的稀中性水溶液（0.01 M）通常仅产生少量二聚体和痕量寡聚物；大部分pN水解生成核苷5'-单磷酸（5'NMP）。早期对pN在高浓度水溶液（高达1.4 M）中反应的研究表明，正如预期的那样，随着pN浓度的增加，缩合产物的产率百分比增加，水解产物的产率相应降低（卡纳瓦里奥蒂，1997年）。在这里，我们报告了在相同总核苷酸浓度下，与一种、两种或三种反应性组分反应的产物分布情况。用作底物的pN是核苷5'-磷酸2-甲基咪唑酯，即2-MeImpN，其中N = 胞苷（C）、尿苷（U）或鸟苷（G）。反应以自缩合的形式进行，即仅一种核苷酸，在三种二元U、C、U、G和C、G混合物中有两种组分，在三元U、C、G混合物中有三种组分。产物有5'NMP、5',5'-焦磷酸、2',5'-、3',5'-连接的二聚体、环状二聚体以及少量较长的寡聚物。令人惊讶的发现是，在相同条件下，包括相同的总单体浓度，不同反应的产物分布差异很大，这很可能是由于分子间相互作用因成分不同而发生变化。更出乎意料的是观察到的趋势，即U、C、G混合物的反应产生的核苷酸间连接二聚体产率最高，而自缩合反应产生的最少，二元混合物的反应产率则介于两者之间。值得注意的是，核苷酸间连接二聚体产率百分比大约增加两倍，并非由于浓度效应或催化剂，而是由于系统从单一组分增加到两种和三种组分导致的复杂性增加。这些观察结果或许提供了一个例子，说明相对简单化学系统中复杂性的增加如何导致物质的组织，进而导致化学进化。文中还讨论了前生物化学与假定的RNA世界之间可能的联系。
