A powerful new biochemical platform stimulates the study of a family of enzymes that are promising targets for cancer treatment.
Posted today in Scientific achievementsThe new method provides a high-resolution view of how these enzymes, called lysine methyltransferase, selectively label proteins with chemical labels that alter their functions. Because of their central role in all aspects of health and disease, proteins and molecules that change and interact with them are often the targets of therapeutic development.
The platform was developed by the Scott Rothbarth Scott Rothbard (Van D. Andel Research Institute) in collaboration with EpiCypher, Inc.
“This technology helps us identify protein interaction networks for this little-known family of enzymes based on chemical labeling,” said Rothbart. “Several inhibitors of these enzymes are currently in the clinical pipeline for the treatment of cancer. Determining the spectrum of their activity is crucial for understanding how these drugs work and for selecting reliable biomarkers to track their activity in patients. ”
People have about 20,000 genes that contain instructions for making proteins, molecular workhorses that are responsible for carrying out every process in the human body, from helping with digestive digestion to controlling the communication between cells.
Once a protein is constructed, its function is often modified by the addition of small chemical labels that define proteins, where to go into the cell, and when to do its work. There are over 100 different types of these tags, including the addition of methyl groups to lysine amino acid.
Using their new technique, the team found that many other proteins could be labeled with lysine methylation than previously thought.
“Our research shows that what we know about lysine methylation is only the tip of the iceberg,” says Evan Cornette, Ph.D., the first author of the study and post-doctoral candidate at the Rothbart laboratory at the Institute. “The method we developed will allow us to identify new targets across the entire lysine-methyltransferase complex in humans and thereby help us and other people determine which cancers and other diseases may be useful for treatment targeting this class of enzymes.”
This technology is the latest achievement thanks to the collaboration between the Rothbarth laboratory and the EpiCypher. Their work was supported by several National Institutes of Health (NIU), Small Business Innovation Awards (SBIR). SBIR, commonly known as the Seed Fund of America, provides research-funded grants for small businesses by the federal government in an effort to invest in a US-led discovery. The SBIR program supports small businesses in the biotechnology sector, focusing on strategies that have a high potential for significant impact and successful commercialization in the medical field. SBIR is committed to expanding academic and industry partnerships to bridge the gap between basic science and clinical advances and become important stimulators of technological innovation.
“The beauty of this technology is its simplicity and throughput, which is staggering compared to modern approaches based on mass spectrometry,” said Martis Coles, Ph.D., chief business officer at EpiCypher and co-author of the study. "We are pleased to use this technology to help drug developers identify new therapeutic targets and even identify optimal target substrates for high-throughput screening."
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