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Study: High throughput platform allows mapping of emerging cancer targets – (Details)

The powerful new biochemical platform feeds enzyme family studies that are promising targets for cancer treatment.

Posted today at Scientific advances, the new method provides a high resolution view, as these enzymes, called lysine methyltransferase, selectively mark proteins with chemical tags that alter their function. Because of their central role in all aspects of health and disease, the proteins and molecules that regulate and interact with them are often targets for therapeutic development.

This platform was developed by Scott Rothbartem, Ph.D., in collaboration with EpiCypher, Inc.

"This technology helps us to set up protein-binding networks for this family of enzymes based on chemical labeling," said Rothbart. "Several inhibitors of these enzymes are currently in the clinical development pipeline for the treatment of cancer. Defining the spectrum of their activity is critical to understanding exactly how these drugs work and to selecting reliable biomarkers to monitor their activity in patients."

People have roughly 20,000 genes that contain guidelines for protein production, molecular workers who are responsible for carrying out every process in the human body, from helping to digest food to managing cell communication.

Once the protein is built up, its function is often modified by the addition of small chemical tags that instruct proteins, where to go to the cell and when to perform their work. There are more than 100 different types of these tags, including the addition of methyl groups to the amino acid lysine.

Using the new technique, they have found that many other proteins can be labeled with methylation of lysine than previously thought.

"Our study suggests that what we currently know about lysine methylation is just the tip of the glacier," said Evan Cornett, Ph.D., the first author of the study and a postdoctoral researcher at the Rothbart Laboratory at the Institute. "The method we developed allows us to identify new targets in the whole human lysine-methyltransferase population and help us and other people identify which cancers and other illnesses could benefit from treatment for this class of enzymes."

This technology is the latest advance, resulting from collaboration between Rothbart and EpiCypher. Their work has been supported by several awards by the National Business Institute (NIH) Small Business Innovation Research (SBIR). Together known as the US seed fund, SBIR provides federally funded research grants to small businesses in an effort to invest in American leadership. SBIR supports small businesses in the biotech industry focusing on strategies that have a high potential for significant impact and successful commercialization in medicine. SBIR grants advocate increased partnerships between the academic and industrial sectors to bridge the gap between fundamental science and clinical advancement and are important stimulators of technological innovation.

"The beauty of this technology is its simplicity and permeability, which is stunning compared to current mass spectrometer-based approaches," says Martis Cowles, Ph.D., chief marketing officer of EpiCypher and co-author of the study. "We are thrilled to use this technology to help drug developers identify new therapeutic targets and even identify optimal target substrates for screening high-throughput inhibitors."


Van Andel Research Institute. .

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