河南师范大学王红磊团队报道了化学O-ADP-核糖基化——NAD+到ADPr肽/蛋白质的合成和生物偶联。相关研究成果发表在2025年1月6日出版的《德国应用化学》。

ADP核糖基化是一种复杂的翻译后修饰，涉及关键的各种健康和疾病状态有关的生理过程。对ADP核糖基化的日益增长的兴趣，需要直接有效的合成方法来制备ADP核糖基肽/蛋白质。

该文中，研究人员报告了烟酰胺腺嘌呤二核苷酸（NAD⁺）与醇，在离子液体组合的促进下发生的简单反应，α：β比在88:12至99:1之间，产率高达94%，并且具有可切换的构型选择性。

这种方法大大简化了ADP核糖基化肽和蛋白质的生产，实现了多样化的应用。它能够详细研究侧链结构-活性关系，促进ADP核糖基与蛋白质的两步可点击结合，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。

附：英文原文

Title: Chemical O-ADP-Ribosylations: Synthesis and Bioconjugation of ADPr-Peptides/Proteins from NAD+

Author: Lingjun Li, Yanbo You, Anlian Zhu, Dongshuang Fan, Honglei Wang

Issue&Volume: 2025-01-06

Abstract: 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+.

DOI: 10.1002/anie.202418321

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202418321