title: Investigation of the action of poly(ADP-ribose)-synthesising enzymes on NAD+analogues.
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.
authors.affiliation: Department of Chemistry, University of Konstanz, Universitätsstraße 10, 78457 Konstanz, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Wallrodt
authors.affiliation: Department of Chemistry, University of Konstanz, Universitätsstraße 10, 78457 Konstanz, Germany.
authors.forename: Edward L
authors.initials: EL
authors.lastname: Simpson
authors.affiliation: Department of Chemistry, University of Konstanz, Universitätsstraße 10, 78457 Konstanz, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Marx
keywords: ARTD; NAD+; click chemistry; poly(ADP-ribose); posttranslational modification