Activity-based protein profiling of protein arginine methyltransferase 1
UMass Chan Affiliations
Department of Biochemistry and Molecular PharmacologyDocument Type
Journal ArticlePublication Date
2011-10-21Keywords
Breast NeoplasmsCell Line, Tumor
*Drug Design
Enzyme Inhibitors
Female
Humans
Inhibitory Concentration 50
Protein-Arginine N-Methyltransferases
Repressor Proteins
Biochemistry
Enzymes and Coenzymes
Medicinal-Pharmaceutical Chemistry
Therapeutics
Metadata
Show full item recordAbstract
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 approximately 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.Source
ACS Chem Biol. 2011 Oct 21;6(10):1127-35. doi: 10.1021/cb2001473. Epub 2011 Aug 23. Link to article on publisher's siteDOI
10.1021/cb2001473Permanent Link to this Item
http://hdl.handle.net/20.500.14038/50034Notes
At the time of publication, Paul Thompson was not yet affiliated with UMass Medical School.
Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1021/cb2001473