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Fluorescent Biosensor

To Aid in Drug Development

Fluorescent Biosensor

Researchers at Carnegie Mellon University have developed a new fluorescent biosensor that could aid in the development of an important class of drugs that target a crucial class of proteins called G protein-coupled receptors (GPCRs).

"Drugs that target GPCRs make up approximately 30 percent of all pharmaceuticals currently on the market, including some of the most prescribed drugs," said Jonathan Jarvik, the Carnegie Mellon Biological Sciences professor who led the effort to develop the GPCR biosensor.

GPCRs are popular drug targets because of the pivotal role they play in cells' chemical communication circuits. The circuits are responsible for regulating functions critical to health, including heart and lung function, mood, cognition and memory, digestion and the inflammatory response.

Found in the cell membrane, GPCRs interact with molecules responsible for cellular communication such as neurotransmitters and hormones. When one of the receptors encounters such a molecule, it relays a signal across the cell membrane that, in turn, initiates a response. After the response is triggered, the receptor retreats from the membrane into the cell's interior.

Invented by Carnegie Mellon's Molecular and Biosensor Imaging Center (MBIC), fluoromodules are probes that allow scientists to monitor the activities of individual proteins found in living cells in real-time.

The probes are made up of two components: a fluorogen-activating protein (FAP) and a non-fluorescent dye called a fluorogen. The FAP is attached to the protein that is being studied, and the fluorogen is engineered to bind to the FAP. When the two meet, they cast off a glow that can be detected using a variety of methods, alerting researchers to the protein's location and activity.

In the current study, which is published in the July issue of the Journal of Biomolecular Screening, Jarvik and colleagues engineered a fluoromodule that would readily determine when GPCR retreats from the cell membrane.

The new biosensor is notable, Jarvik said, because it can be scaled to screen large numbers of molecules to identify new drug leads.

The researchers are hopeful that this technology can be generalized across other receptors and cell-surface proteins, and are currently researching its broader applications.

This research was funded by the National Institutes of Health (NIH). MBIC is one of the NIH's National Technology Centers for Networks and Pathways.

Related Links: Biological Sciences  |  MBIC

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