2. Academic Validation
  3. Bioorthogonally Functionalized NAD(+) Analogues for In-Cell Visualization of Poly(ADP-Ribose) Formation

Bioorthogonally Functionalized NAD(+) Analogues for In-Cell Visualization of Poly(ADP-Ribose) Formation

  • Angew Chem Int Ed Engl. 2016 Jun 27;55(27):7660-4. doi: 10.1002/anie.201600464.
Sarah Wallrodt 1,  Annette Buntz 1,  Yan Wang 1,  Andreas Zumbusch 1,  Andreas Marx 2
Affiliations

Affiliations

  • 1 Department of Chemistry, University of Konstanz, Universitätsstraße 10, 78457, Konstanz, Germany.
  • 2 Department of Chemistry, University of Konstanz, Universitätsstraße 10, 78457, Konstanz, Germany. [email protected].
PMID: 27080423 DOI: 10.1002/anie.201600464
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.

Keywords

ADP-ribosylation; bioorthogonal reactions; poly(ADP-ribose); protein modification.

Figures
Products