Development of a Novel Photoreversible Ca2+ Chelator to Mimic Calcium Signaling

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The development of a photoreversible, calcium-selective chelator that will effectively mimic a wide range of physiological calcium signaling patterns in vitro and in vivo is the focus of this work. While much is known about how calcium oscillations in cells are generated, much less is known about their effect on the activity of individual proteins. This method will be used to decipher the effects of calcium signals on a molecular level, eventually leading to insights about both normal and disease-states in humans. Preliminary studies have shown the molecule above (R6 = H, R3 = CH3) has moderate binding and selectivity for Ca 2+. Specific changes to the structure at R3, R6, and the chelating carboxylates are proposed here to test hypotheses about the calcium binding strength and selectivity and photochromism of this molecule. These structural modifications will include both steric and electronic changes that should affect the ground state stability of the molecule. The effects of structural variations on both metal ion binding and photophysical properties will be examined using 1H NMR and UV spectroscopy.