Seeing citrulline: development of a phenylglyoxal-based probe to visualize protein citrullination.
Department of Biochemistry and Molecular Pharmacology
Medical Subject Headings
Animals; Biological Markers; Citrulline; Hydrolases; Kinetics; Mice; Molecular Probes; Molecular Structure; Phenylglyoxal; Rhodamines
Biochemistry | Enzymes and Coenzymes | Medicinal-Pharmaceutical Chemistry | Therapeutics
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.
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Citation: 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 site
Bicker, Kevin L.; Subramanian, Venkataraman; Chumanevich, Alexander A.; Hofseth, Lorne J.; and Thompson, Paul R., "Seeing citrulline: development of a phenylglyoxal-based probe to visualize protein citrullination." (2012). Thompson Lab Publications. 32.