The study was published October 3, 2012, in the Journal of the American Chemical Society.
The new research focuses on the protein arginine deiminases (PAD), which have been implicated in a number of diseases, including cancer, multiple sclerosis and rheumatoid arthritis. PADs participate in reactions in the body that form the amino acid citrulline in proteins through a process known as citrullination. This modification can have significant effects on the structure and function of the modified proteins.
While abnormally high PAD activity is present in a host of human diseases, the exact role of citrullination in these diseases remains unknown, largely due to the lack of readily available chemical probes to study it.
“We have developed technology to identify biomarkers for a variety of diseases in which you see abnormal PAD activity,” said Paul Thompson, an associate professor in the Department of Chemistry at Scripps Research, who led the study. “This identification of potential biomarkers in animal models of ulcerative colitis is really the first step in a much larger effort. We want to push forward into rheumatoid arthritis and cancer to look for different diagnostic markers in these disease situations.”
In the new study, the scientists describe a chemical probe called rhodamine‐phenylglyoxal (Rh‐PG), which tags citrulline-containing proteins with a fluorescent imaging compound.
According to Thompson, the next step will be to produce further generations of this chemical probe to isolate the biomarker proteins and determine their sites of modification, as well as to quantify the extent of the citrullination.
The first author of the study, “Seeing Citrulline: Development of a Phenylglyoxal‐Based Probe to Visualize Protein Citrullination,” is Kevin L. Bicker of Scripps Research. Other authors include Venkataraman Subramanian of Scripps Research and Alexander A. Chumanevich and Lorne J. Hofseth of the University of South Carolina. For more information, see http://pubs.acs.org/doi/abs/10.1021/ja308871v
The study was supported by the National Institutes of Health (grants GM079357 and CA151304) and Scripps Research.
About The Scripps Research Institute
The Scripps Research Institute is one of the world’s largest independent, not-for-profit organizations focusing on research in the biomedical sciences. Over the past decades, Scripps Research has developed a lengthy track record of major contributions to science and health, including laying the foundation for new treatments for cancer, rheumatoid arthritis, hemophilia, and other diseases. The institute employs about 3,000 people on its campuses in La Jolla, CA, and Jupiter, FL, where its renowned scientists—including three Nobel laureates—work toward their next discoveries. The institute’s graduate program, which awards Ph.D. degrees in biology and chemistry, ranks among the top ten of its kind in the nation. For more information, see www.scripps.edu.
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