Title

Seeing citrulline: development of a phenylglyoxal-based probe to visualize protein citrullination.

UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology

Publication Date

10-17-2012

Document Type

Article

Subjects

Animals; Biological Markers; Citrulline; Hydrolases; Kinetics; Mice; Molecular Probes; Molecular Structure; Phenylglyoxal; Rhodamines

Disciplines

Biochemistry | Enzymes and Coenzymes | Medicinal-Pharmaceutical Chemistry | Therapeutics

Abstract

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.

DOI of Published Version

10.1021/ja308871v

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 site

Journal/Book/Conference Title

Journal of the American Chemical Society

Comments

At the time of publication, Paul Thompson was not yet affiliated with UMass Medical School.

Related Resources

Link to Article in PubMed

Link to Full Text

Share

COinS