Zhang Lei, Zhang Xiao-Nan, Ansari Arshad J, Zhang Yong
Department of Pharmacology and Pharmaceutical Sciences, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089, USA.
Department of Chemistry, Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA 90089, USA.
Tetrahedron. 2024 Dec 1;168. doi: 10.1016/j.tet.2024.134361. Epub 2024 Nov 6.
Protein adenosine diphosphate (ADP)-ribosylation participates in various pivotal cellular events. Its readers and erasers play key roles in modulating ADP-ribosylation-based signaling pathways. Unambiguous assignments of readers and erasers to individual ADP-ribosylated proteins provide insightful knowledge on ADP-ribosylation biology and require the development of tools and technologies for this goal. Herein, we report the design and the synthesis of a nicotinamide adenine dinucleotide (NAD) carrying a photoactive and a clickable group. Functioning as a substrate for poly-ADP-ribosylation (PARylation), this NAD mimic with dually modified adenine enables covalent crosslinking and labeling of proteins bound to PARylation, representing a new photoaffinity probe for studying this critical post-translational modification.
蛋白质二磷酸腺苷（ADP）-核糖基化参与各种关键的细胞事件。其识别蛋白和去修饰酶在调节基于ADP-核糖基化的信号通路中起关键作用。将识别蛋白和去修饰酶明确分配给单个ADP-核糖基化蛋白，可为ADP-核糖基化生物学提供有深刻见解的知识，为此需要开发相关工具和技术。在此，我们报告了一种携带光活性基团和可点击基团的烟酰胺腺嘌呤二核苷酸（NAD）的设计与合成。这种具有双重修饰腺嘌呤的NAD类似物作为多聚ADP-核糖基化（PARylation）的底物，能够与结合到PARylation的蛋白质进行共价交联和标记，代表了一种用于研究这种关键翻译后修饰的新型光亲和探针。
