Seeing citrulline: development of a phenylglyoxal-based probe to visualize protein citrullination.
Authors
Bicker, Kevin L.Subramanian, Venkataraman
Chumanevich, Alexander A.
Hofseth, Lorne J.
Thompson, Paul R
UMass Chan Affiliations
Department of Biochemistry and Molecular PharmacologyDocument Type
Journal ArticlePublication Date
2012-10-17Keywords
AnimalsBiological Markers
Citrulline
Hydrolases
Kinetics
Mice
Molecular Probes
Molecular Structure
Phenylglyoxal
Rhodamines
Biochemistry
Enzymes and Coenzymes
Medicinal-Pharmaceutical Chemistry
Therapeutics
Metadata
Show full item recordAbstract
Protein arginine deiminases (PADs) catalyze the hydrolysis of peptidyl arginine to form peptidyl citrulline. Abnormally high PAD activity is observed in a host of human diseases, but the exact role of protein citrullination in these diseases and the identities of specific citrullinated disease biomarkers remain unknown, largely because of the lack of readily available chemical probes to detect protein citrullination. For this reason, we developed a citrulline-specific chemical probe, rhodamine-phenylglyoxal (Rh-PG), which we show can be used to investigate protein citrullination. This methodology is superior to existing techniques because it possesses higher throughput and excellent sensitivity. Additionally, we demonstrate that this probe can be used to determine the kinetic parameters for a number of protein substrates, monitor drug efficacy, and identify disease biomarkers in an animal model of ulcerative colitis that displays aberrantly increased PAD activity.Source
J Am Chem Soc. 2012 Oct 17;134(41):17015-8. doi: 10.1021/ja308871v. Epub 2012 Oct 3. Link to article on publisher's siteDOI
10.1021/ja308871vPermanent Link to this Item
http://hdl.handle.net/20.500.14038/50022Notes
At the time of publication, Paul Thompson was not yet affiliated with UMass Medical School.
Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1021/ja308871v