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Analytical Chemistry

Fluorescence Probe For Citrullination

Monitoring technique could aid understanding of disease-related citrulline protein modifications

by Stu Borman
October 15, 2012 | A version of this story appeared in Volume 90, Issue 42

PROTEIN PROBES
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Credit: J. Am. Chem. Soc.
Probes composed of phenylglyoxal (black) and rhodamine (red) bind selectively to citrullines (blue) in the presence of underivatized arginines (green) on proteins (such as histones, gray) and can thus be used to detect citrulline modifications.
These are probes, composed of phenylglyoxal (black) and rhodamine (red), bind selectively to citrullines (blue) in the presence of underivatized arginines (green) on proteins (like histones, gray) and can thus be used to detect citrullination.
Credit: J. Am. Chem. Soc.
Probes composed of phenylglyoxal (black) and rhodamine (red) bind selectively to citrullines (blue) in the presence of underivatized arginines (green) on proteins (such as histones, gray) and can thus be used to detect citrulline modifications.

A new technique for detecting citrulline groups, a type of posttranslational protein modification associated with a variety of human diseases, has speed and sensitivity advantages over previous techniques (J. Am. Chem. Soc., DOI: 10.1021/ja308871v). The method could lead to a deeper understanding of citrullination and aid drug development for associated illnesses. Citrullines are amino acids generated from arginine residues by protein arginine deiminases (PADs), which have abnormally high activity in rheumatoid arthritis, ulcerative colitis, Alzheimer’s disease, multiple sclerosis, cancer, and other conditions. The role of citrullination isn’t well understood, in part because colorimetric detection of citrulline has low sensitivity and antibody-based detection techniques are expensive and slow. Paul R. Thompson of Scripps Florida and coworkers devised a phenylglyoxal-based citrulline test with fluorescence detection. The method is fast and highly sensitive, and it can be used by most researchers because the reagents and instruments needed for detection are available in virtually all biochemically focused laboratories, the researchers note. They used the technology to identify disease biomarkers in mice with ulcerative colitis and believe it could aid the search for therapeutic PAD inhibitors.

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