Division of Biophysics, Institute of Experimental Physics, Faculty of Physics, University of Warsaw, Pasteura 5, 02-093 Warsaw, Poland.
Molecules. 2019 Nov 19;24(22):4187. doi: 10.3390/molecules24224187.
Nicotinamide adenine dinucleotide (NAD) serves as an essential redox co-factor and mediator of multiple biological processes. Besides its well-established role in electron transfer reactions, NAD serves as a substrate for other biotransformations, which, at the molecular level, can be classified as protein post-translational modifications (protein deacylation, mono-, and polyADP-ribosylation) and formation of signaling molecules (e.g., cyclic ADP ribose). These biochemical reactions control many crucial biological processes, such as cellular signaling and recognition, DNA repair and epigenetic modifications, stress response, immune response, aging and senescence, and many others. However, the links between the biological effects and underlying molecular processes are often poorly understood. Moreover, NAD has recently been found to tag the 5'-ends of some cellular RNAs, but the function of these NAD-capped RNAs remains largely unrevealed. Synthetic NAD analogs are invaluable molecular tools to detect, monitor, structurally investigate, and modulate activity of NAD-related enzymes and biological processes in order to aid their deeper understanding. Here, we review the recent advances in the design and development of NAD analogs as probes for various cellular NAD-related enzymes, enzymatic inhibitors with anticancer or antimicrobial therapeutic potential, and other NAD-related chemical biology tools. We focus on research papers published within the last 10 years.
烟酰胺腺嘌呤二核苷酸（NAD）作为一种重要的氧化还原辅助因子和多种生物过程的介质。除了在电子转移反应中众所周知的作用外，NAD 还作为其他生物转化的底物，从分子水平上可以分为蛋白质翻译后修饰（蛋白质脱酰基、单聚和多聚 ADP-核糖基化）和信号分子的形成（例如，环状 ADP 核糖）。这些生化反应控制着许多关键的生物过程，如细胞信号转导和识别、DNA 修复和表观遗传修饰、应激反应、免疫反应、衰老和衰老等。然而，生物效应和潜在分子过程之间的联系往往知之甚少。此外，最近发现 NAD 标记了一些细胞 RNA 的 5' 端，但这些 NAD 帽 RNA 的功能在很大程度上仍未被揭示。合成 NAD 类似物是非常有价值的分子工具，可用于检测、监测、结构研究和调节与 NAD 相关的酶和生物过程的活性，以帮助深入了解它们。在这里，我们回顾了过去 10 年来设计和开发 NAD 类似物作为各种细胞 NAD 相关酶的探针、具有抗癌或抗菌治疗潜力的酶抑制剂以及其他 NAD 相关化学生物学工具的最新进展。我们重点介绍了在过去 10 年内发表的研究论文。
