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

开发新型光可逆 Ca2 螯合剂来模拟钙信号传导

• 批准号: 7454137
• 负责人: ALISON MCCURDY
• 金额: $ 49.7万
• 依托单位: CALIFORNIA STATE UNIVERSITY LOS ANGELES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7454137
• 关键词: Affect; Affinity; Binding; Binding Sites; Calcium; Calcium Binding; Calcium Oscillations; Calcium Signaling; Cells; Chelating Agents; Data; Development; Disease; Electronics; Human; In Vitro; Individual; Ligands; Magnesium; Metal Ion Binding; Methods; Modification; Molecular; Nature; Pattern; Physiological; Property; Proteins; Purpose; Range; Reaction; Signal Transduction; Specificity; Spectrum Analysis; Structure; Testing; Upper arm; Variant; Work; carboxylate; design; improved; in vivo; insight; irradiation; novel; scaffold

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.

开发一种光可逆的钙选择性螯合剂，它将有效地模拟体外和体内广泛的生理钙信号模式，是这项工作的重点。虽然我们对细胞中钙振荡是如何产生的了解很多，但对它们对单个蛋白质活性的影响知之甚少。此方法将用于