Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form

Novel inhibitors for PRMT1 discovered by high-throughput screening using activity-based fluorescence polarization

Academic Article
uri icon
  • Overview
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

related to degree

  • Dillon, Myles, Ph.D. in Biology, Scripps Research 2008 - 2013
  • Bachovchin, Daniel A., Ph.D. in Chemistry, Scripps Research 2006 - 2011

authors

  • Dillon, Myles
  • Bachovchin, Daniel A.
  • Brown, S. J.
  • Finn, M.G.
  • Rosen, Hugh
  • Cravatt, Benjamin
  • Mowen, Kerri

publication date

  • July 2012

journal

  • ACS Chemical Biology  Journal

abstract

  • Protein arginine methyltransferases (PRMTs) catalyze the posttranslational methylation of arginine using S-adenosylmethionine (SAM) as a methyl-donor. The PRMT family is widely expressed and has been implicated in biological functions such as RNA splicing, transcriptional control, signal transduction, and DNA repair. Therefore, specific inhibitors of individual PRMTs have potentially significant research and therapeutic value. In particular, PRMT1 is responsible for >85% of arginine methyltransferase activity, but currently available inhibitors of PRMT1 lack specificity, efficacy, and bioavailability. To address this limitation, we developed a high-throughput screening assay for PRMT1 that utilizes a hyper-reactive cysteine within the active site, which is lacking in almost all other PRMTs. This assay, which monitors the kinetics of the fluorescence polarization signal increase upon PRMT1 labeling by a rhodamine-containing cysteine-reactive probe, successfully identified two novel inhibitors selective for PRMT1 over other SAM-dependent methyltransferases.

subject areas

  • Drug Discovery
  • Enzyme Inhibitors
  • Fluorescence Polarization
  • High-Throughput Screening Assays
  • Maleimides
  • Protein-Arginine N-Methyltransferases
  • Repressor Proteins
scroll to property group menus

Identity

PubMed Central ID

  • PMC3401332

International Standard Serial Number (ISSN)

  • 1554-8929

Digital Object Identifier (DOI)

  • 10.1021/cb300024c

PubMed ID

  • 22506763
scroll to property group menus

Additional Document Info

start page

  • 1198

end page

  • 1204

volume

  • 7

issue

  • 7

©2021 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support