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For many drugs there’s a fine line between efficacy and toxicity, and maintaining the right dose requires close monitoring of the drug concentration. A new family of semisynthetic bioluminescent proteins could bring that monitoring to the patient’s bedside. The sensors, made by Kai Johnsson of ETH Lausanne and coworkers, have three components: a receptor protein that binds the drug of interest, the bioluminescent protein luciferase, and a synthetic portion that contains a ligand for the receptor protein and a cyanine fluorophore (Nat. Chem. Biol. 2014, DOI: 10.1038/nchembio.1554). When the ligand binds the receptor protein, the connection brings the fluorophore close enough to the luciferase to allow bioluminescent resonance energy transfer (BRET) to excite the fluorophore. At sufficient concentrations, the drug of interest displaces the ligand and causes BRET to decrease. The researchers performed the analysis by spotting blood serum on paper and taking a picture with a digital camera. They determined the concentration of the drug from the ratio of the blue light emitted by the luciferase and the red light emitted by the fluorophore. The researchers developed sensors for several drugs, including the anticancer agent methotrexate.
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