Bioorthogonally Functionalized NAD(+) Analogues for In-Cell Visualization of Poly(ADP-Ribose) Formation.
Angewandte Chemie (International ed. in English)
confidence
Key findings
Developed bioorthogonally functionalized NAD(+) analogues for in-cell visualization of PARylation; tool for imaging PARylation in vitro and in cells.
View source on PubMed (PMID 27080423) ↗
- Sample size
- Not reported
- Population
- In vitro and cellular models (not human)
- Dosing
- Not reported
- Duration
- Not reported
- Route
- Not reported
- Blinding
- not_reported
- Controls
- none
- Drug class
- coenzyme
Full abstract
Poly(ADP-ribos)ylation (PARylation) is a major posttranslational modification and signaling event in most eukaryotes. Fundamental processes like DNA repair and transcription are coordinated by this transient polymer and its binding to proteins. ADP-ribosyltransferases (ARTs) build complex ADP-ribose chains from NAD(+) onto various acceptor proteins. Molecular studies of PARylation thus remain challenging. Herein, we present the development of bioorthogonally functionalized NAD(+) analogues for the imaging of PARylation in vitro and in cells. Our results show that 2-modified NAD(+) analogues perform remarkably well and can be applied to the in-cell visualization of PARylation simultaneously in two colors. This tool gives insight into the substrate scope of ARTs and will help to further elucidate the biological role of PARylation by offering fast optical, multichannel read-outs.