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An NAD+ with Dually Modified Adenine for Labeling ADP-Ribosylation-Specific Proteins
Lei Zhang1, Xiao-Nan Zhang1, Arshad J Ansari1
1Department of Pharmacology and Pharmaceutical Sciences, Alfred E. Mann School of Pharmacy and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089, USA.
Abstract:
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.
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