Calcium Signaling: A Novel Photoreversible Ca2+ Chelator

开发一种光可逆的、钙选择性的螯合剂，在体外和体内有效地模拟多种生理钙信号模式，是这项工作的重点。虽然人们对细胞中的钙振荡是如何产生的知道很多，但对它们对单个蛋白质活性的影响却知之甚少。此方法将用于 在分子水平上破译钙信号的影响，最终导致对人类正常和疾病状态的洞察。 初步研究表明，上述分子(R6=H，R3=CH3)对钙离子具有中等的结合和选择性。这里提出了对R3、R6和螯合羧酸盐结构的特殊改变，以检验关于该分子的钙结合强度、选择性和光致变色性的假设。这些结构修饰将包括空间和电子变化，这些变化应该会影响分子的基态稳定性。结构变化对金属离子结合和光物理性质的影响将用~1H核磁共振和紫外光谱来检验。

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.