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Small-Molecule Screening Assay for Mono-ADP-Ribosyltransferases.

  • Teemu Haikarainen
  • , Sudarshan Murthy
  • , Mirko Maksimainen
  • , Lari Lehtiö*
  • *Corresponding author for this work
  • University of Oulu
  • Aalto University

Research output: Chapter in Book/Report/Conference proceedingChapter or book articleScientificpeer-review

Abstract

Mono-ADP-ribosyltransferases of the PARP/ARTD enzyme family are enzymes catalyzing the transfer of a single ADP-ribose unit to target proteins. The enzymes have various roles in vital cellular processes such as DNA repair and transcription, and many of the enzymes are linked to cancer-relevant functions. Thus inhibition of the enzymes is a potential way to discover and develop new drugs against cancer. Here we describe an activity-based screening assay for mono-ADP-ribosyltransferases. The assay utilizes the natural substrate of the enzymes, NAD<sup>+</sup>, and it is based on chemically converting the leftover substrate to a fluorophore and measuring its relative concentration after the enzymatic reaction. The assay is homogenous, robust, and cost-effective and, most importantly, applicable to mono-ADP-ribosyltransferases as well as poly-ADP-ribosyltransferases for screening of small-molecule inhibitors against the enzymes.
Original languageEnglish
Title of host publicationADP-ribosylation and NAD+ Utilizing Enzymes
Subtitle of host publicationMethods and Protocols
PublisherSpringer
Pages237-244
Number of pages8
ISBN (Electronic)978-1-4939-8588-3
ISBN (Print)978-1-4939-8587-6, 978-1-4939-9335-2
DOIs
Publication statusPublished - 1 Jan 2018
MoE publication typeA3 Part of a book or another research book

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

  1. SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well-being

Keywords

  • ARTD
  • Inhibitor
  • Mono-ADP-ribosyltransferase
  • PARP
  • Screening assay

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