Institute of Biochemistry, University of Greifswald, Felix-Hausdorff-Str. 4, 17487 Greifswald, Germany.
Molecules. 2024 Aug 10;29(16):3788. doi: 10.3390/molecules29163788.
Nicotinamide is an important functional compound and, in the form of nicotinamide adenine dinucleotide (NAD), is used as a co-factor by protein-based enzymes to catalyze redox reactions. In the context of the RNA world hypothesis, it is therefore reasonable to assume that ancestral ribozymes could have used co-factors such as NAD or its simpler analog nicotinamide riboside (NAR) to catalyze redox reactions. The only described example of such an engineered ribozyme uses a nicotinamide moiety bound to the ribozyme through non-covalent interactions. Covalent attachment of NAR to RNA could be advantageous, but the demonstration of such scenarios to date has suffered from the chemical instability of both NAR and its reduced form, NARH, making their use in oligonucleotide synthesis less straightforward. Here, we review the literature describing the chemical properties of the oxidized and reduced species of NAR, their synthesis, and previous attempts to incorporate either species into RNA. We discuss how to overcome the stability problem and succeed in generating RNA structures incorporating NAR.
烟酰胺是一种重要的功能化合物，以烟酰胺腺嘌呤二核苷酸（NAD）的形式作为蛋白基酶的辅助因子，催化氧化还原反应。因此，在 RNA 世界假说的背景下，有理由假设原始核酶可能使用 NAD 或其更简单的类似物烟酰胺核苷（NAR）等辅助因子来催化氧化还原反应。唯一描述的这种经过工程改造的核酶的例子是使用通过非共价相互作用结合到核酶上的烟酰胺部分。NAR 与 RNA 的共价连接可能是有利的，但迄今为止，此类方案的演示受到 NAR 及其还原形式 NARH 的化学不稳定性的影响，使得它们在寡核苷酸合成中的应用不太直接。在这里，我们回顾了描述 NAR 的氧化和还原形式的化学性质、它们的合成以及以前将它们掺入 RNA 中的尝试的文献。我们讨论了如何克服稳定性问题并成功生成包含 NAR 的 RNA 结构。
