You Yanbo, Zhu Anlian, Fan Dongshuang, Wang Honglei, Li Lingjun
School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, Henan, 453007, China.
Collaborative Innovation Center of Henan Province for Green Manufacturing of Fine Chemicals, School of Chemistry and Chemical Engineering, Key laboratory of Green Chemical Media and Reactions, Ministry of Education, Henan Normal University, Xinxiang, Henan, 453007, China.
Angew Chem Int Ed Engl. 2025 Feb 3;64(6):e202418321. doi: 10.1002/anie.202418321. Epub 2025 Jan 15.
ADP-ribosylation is a complex post-translational modification involved in key physiological processes and associated with various health and disease states. The growing interest in ADP-ribosylation necessitates straightforward and efficient synthetic methods for the preparation of ADP-ribosylated peptides/proteins. In this study, we report a facile reaction between nicotinamide adenine dinucleotide (NAD) and alcohols promoted by a combination of ionic liquids, yielding up to 94 % with α : β ratios ranging from 88 : 12 to 99 : 1 and a switchable configuration selectivity. This method significantly simplifies the production of ADP-ribosylated peptides and proteins, enabling diverse applications. It allows detailed investigation of side-chain structure-activity relationships, facilitates two-step clickable conjugation of ADP-ribosyl groups to proteins, and, for the first time, enables non-enzymatic synthesis of well-defined ADP-ribosylated peptides/proteins from natural counterparts and NAD.
ADP-核糖基化是一种复杂的翻译后修饰，参与关键的生理过程，并与各种健康和疾病状态相关。对ADP-核糖基化的兴趣日益增加，因此需要直接有效的合成方法来制备ADP-核糖基化的肽/蛋白质。在本研究中，我们报道了一种由离子液体组合促进的烟酰胺腺嘌呤二核苷酸（NAD）与醇之间的简便反应，产率高达94%，α:β比例范围为88:12至99:1，且具有可切换的构型选择性。该方法显著简化了ADP-核糖基化肽和蛋白质的生产，使其具有多种应用。它允许详细研究侧链结构-活性关系，促进ADP-核糖基与蛋白质的两步可点击共轭，并且首次实现了从天然对应物和NAD非酶合成明确的ADP-核糖基化肽/蛋白质。
