Format

Send to:

Choose Destination
See comment in PubMed Commons below
ACS Chem Biol. 2011 Oct 21;6(10):1127-35. doi: 10.1021/cb2001473. Epub 2011 Aug 23.

Activity-based protein profiling of protein arginine methyltransferase 1.

Author information

  • 1Department of Chemistry, The Scripps Research Institute, Jupiter, Florida 33458, United States.

Abstract

The protein arginine methyltransferases (PRMTs) are SAM-dependent enzymes that catalyze the mono- and dimethylation of peptidyl arginine residues. PRMT1 is the founding member of the PRMT family, and this isozyme is responsible for methylating ∼85% of the arginine residues in mammalian cells. Additionally, PRMT1 activity is aberrantly upregulated in heart disease and cancer. As a part of a program to develop isozyme-specific PRMT inhibitors, we recently described the design and synthesis of C21, a chloroacetamidine bearing histone H4 tail analogue that acts as an irreversible PRMT1 inhibitor. Given the covalent nature of the interaction, we set out to develop activity-based probes (ABPs) that could be used to characterize the physiological roles of PRMT1. Herein, we report the design, synthesis, and characterization of fluorescein-conjugated C21 (F-C21) and biotin-conjugated C21 (B-C21) as PRMT1-specific ABPs. Additionally, we provide the first evidence that PRMT1 activity is negatively regulated in a spatial and temporal fashion.

PMID:
21838253
[PubMed - indexed for MEDLINE]
PMCID:
PMC3199286
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for American Chemical Society Icon for PubMed Central
    Loading ...
    Write to the Help Desk