Investigation of the action of poly(ADP-ribose)-synthesising enzymes on NAD+ analogues.
Beilstein journal of organic chemistry
confidence
Key findings
Comparative substrate scope study of NAD+ analogues for poly(ADP-ribose)-synthesising ARTD enzymes; no clinical/biological endpoints reported.
View source on PubMed (PMID 28382184) ↗
- Sample size
- Not reported
- Population
- In vitro enzyme studies (ARTD1, ARTD2, ARTD5, ARTD6)
- Dosing
- NAD+ analogues
- Duration
- Not reported
- Route
- In vitro
- Blinding
- not_reported
- Controls
- not_reported
- Drug class
- coenzyme
Full abstract
ADP-ribosyl transferases with diphtheria toxin homology (ARTDs) catalyse the covalent addition of ADP-ribose onto different acceptors forming mono- or poly(ADP-ribos)ylated proteins. Out of the 18 members identified, only four are known to synthesise the complex poly(ADP-ribose) biopolymer. The investigation of this posttranslational modification is important due to its involvement in cancer and other diseases. Lately, metabolic labelling approaches comprising different reporter-modified NAD+ building blocks have stimulated and enriched proteomic studies and imaging applications of ADP-ribosylation processes. Herein, we compare the substrate scope and applicability of different NAD+ analogues for the investigation of the polymer-synthesising enzymes ARTD1, ARTD2, ARTD5 and ARTD6. By varying the site and size of the NAD+ modification, suitable probes were identified for each enzyme. This report provides guidelines for choosing analogues for studying poly(ADP-ribose)-synthesising enzymes.