Alzheimer’s, a terminal illness thought to be caused by the misfolding of proteins, is currently the sixth leading cause of death in the United States, and has no known cure. It is our long-term goal to provide improved methods for characterizing proteins so that researchers may further understand proteins, hopefully leading to cures and better treatments for diseases such as Alzheimer’s. This project aims to synthesize a small, rigid nitroxide spin label to be used in electron paramagnetic resonance (EPR) spectroscopy to observe the structure and folding of proteins. Conventionally, gem-dimethyl groups are used in nitroxide spin labels to shield the radical, but due to the rotation of the gem-dimethyl groups, the spin relaxation time (Tm) is shortened. The shorter Tm is, the shorter the distance in the protein the instrument is able to measure. To lengthen Tm, samples must be supercooled by liquid helium, which involves rigorous set up and is highly expensive. By using cyclopropane groups instead of gem-dimethyls, the change in structure may allow for EPR measurements to be taken at temperatures above 77K. This would allow for liquid nitrogen to be used in place of liquid helium, cutting costs significantly and making EPR more accessible. The synthesis of functional 4-azadispiro[2.1.25.23]nonanyl nitroxide will be reported and characterized by electrospray ionization (ESI) mass spectrometry and EPR. Overall, this project may bring us one step closer to taking long and accurate distance measurements at biological temperatures.

New small, rigid nitroxide for site-directed spin labeling of proteins

2019 Spring National Meeting

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