RSC chemical biologyOct 17, 2026

Using NAD+-like molecules to understand how PARP enzymes add ADP-ribose in cells

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Oct 20, 2026

Abstract

Chemically modified NAD⁺ analogues enable significant advancements in understanding ADP-ribosylation.

ADP-ribosylation is a process that modifies proteins to regulate DNA repair and stress responses.
NAD⁺ analogues allow for specific labeling of proteins involved in ADP-ribosylation.
These tools facilitate the capture and enrichment of modified substrates for detailed study.
Recent developments have shifted research from simple detection to exploring underlying mechanisms.
Future directions may focus on enhancing the functionality of these chemical probes.

Simplified

ADP-ribosylation is a NAD⁺-dependent post-translational modification that governs DNA repair, transcription, antiviral defense, and stress adaptation. Its transient and heterogeneous nature, however, has limited mechanistic understanding. Chemically modified NAD⁺ analogues have become indispensable chemical biology tools to overcome these barriers. By functionalizing the NAD⁺ scaffold at positions tolerated by PARP enzymes, these probes enable capture and enrichment of ADP-ribosylated substrates, writer-specific labeling, PAR-chain architecture control, reader identification, and real-time imaging. This Review summarizes recent progress in NAD⁺ analogue development, organized by probe function and biological application. We highlight how these chemical tools have transformed ADP-ribosylation research from descriptive detection toward mechanistic interrogation and discuss future directions for the field.

Full Text

Full text is available at the source.

View Full Text ↗

Using NAD+-like molecules to understand how PARP enzymes add ADP-ribose in cells

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Recent issues from the longevity & aging brief