Biomimetic α-selective ribosylation enables two-step modular synthesis of biologically important ADP-ribosylated peptides

• Published in: Nature communications Vol. 11; no. 1; p. 5600
• Main Authors: Zhu, Anlian, Li, Xin, Bai, Lili, Zhu, Gongming, Guo, Yuanyang, Lin, Jianwei, Cui, Yiwen, Tian, Gaofei, Zhang, Lihe, Wang, Jianji, Li, Xiang David, Li, Lingjun
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 05.11.2020; Nature Publishing Group UK; Nature Portfolio
• Subjects: Adenine; Adenosine diphosphate; ADP-ribosylation; Biomimetics; Chemical synthesis; Chemistry; Ionic liquids; Multidimensional methods; NAD; Nicotinamide; Nicotinamide adenine dinucleotide; Peptides; Proteins; Ribosylation; Tubes
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-19409-1

Abstract The α-type ADP-ribosylated peptides represent a class of important molecular tools in the field of protein ADP-ribosylation, however, they are difficult to access because of their inherent complicated structures and the lack of effective synthetic tools. In this paper, we present a biomimetic α-selective ribosylation reaction to synthesize a key intermediate, α-ADP-ribosyl azide, directly from native β-nicotinamide adenine dinucleotide in a clean ionic liquid system. This reaction in tandem with click chemistry then offers a two-step modular synthesis of α-ADP-ribosylated peptides. These syntheses can be performed open air in eppendorf tubes, without the need for specialized instruments or training. Importantly, we demonstrate that the synthesized α-ADP-ribosylated peptides show high binding affinity and desirable stability for enriching protein partners, and reactivity in post-stage poly ADP-ribosylations. Owing to their simple chemistry and multidimensional bio-applications, the presented methods may provide a powerful platform to produce general molecular tools for the study of protein ADP-ribosylation.