Poly(ADP-ribose) Polymerase pp 491-516

Part of the Methods in Molecular Biology book series (MIMB, volume 780)

Small-Molecule Collection and High-Throughput Colorimetric Assay to Identify PARP1 Inhibitors

  • Elena Kotova
  • Aaron D. Pinnola
  • Alexei V. Tulin
Protocol

Abstract

During the last few years, poly(ADP-ribose)polymerase (PARP) proteins became a very popular target for anticancer treatment. Many PARP inhibitors have been generated and tested by pharmacological industry. However, most of them were designed to disrupt the DNA-dependent PARP1 protein activation pathway and were based on a competition with NAD for a binding site on PARP molecule and, therefore, on disruption of PARP-mediated enzymatic reaction. This limitation resulted in a discovery of mainly nucleotide-like PARP1 inhibitors which may target not only PARP, but also other pathways involving NAD and other nucleotides. Here, we describe a strategy for the identification of PARP inhibitors that target a different pathway, the histone H4-dependent PARP1 activation. Besides the identification of NAD competitors in a small-molecule collection, this approach allows finding novel classes of PARP inhibitors that specifically disrupt H4-based PARP activation.

Key words

PARP1 PARP1 activation PARP1 inhibitor Poly(ADP-ribose) Library of Small-Molecule Inhibitors High-throughput colorimetric assay 

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Elena Kotova
    • 1
  • Aaron D. Pinnola
    • 1
  • Alexei V. Tulin
    • 1
  1. 1.Epigenetics and Progenitor Cells Program, Cancer Biology ProgramFox Chase Cancer CenterPhiladelphiaUSA

Personalised recommendations