Calcium Signaling: A Novel Photoreversible Ca2+ Chelator

钙信号传导：一种新型光可逆 Ca2 螯合剂

• 批准号: 6767013
• 负责人: ALISON MCCURDY
• 金额: $ 15.84万
• 依托单位: CALIFORNIA STATE UNIVERSITY LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6767013
• 关键词: azobenzene; binding sites; biotechnology; calcium flux; calcium ion; chelating agents; chemical chain length; chemical structure function; chemical synthesis; chromatography; intermolecular interaction; molecular probes; nuclear magnetic resonance spectroscopy; photochemistry; pyrans; technology /technique development

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，有效地模拟了广泛的生理钙信号模式在体外和体内是这项工作的重点。虽然人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见解。 初步研究表明，上述分子（R6 = H，R3 = CH 3）对Ca 2+具有中等的结合和选择性。在R3，R6，和螯合羧酸盐的结构的具体变化，提出了在这里测试的钙结合强度和选择性和光致变色的这种分子的假设。这些结构修饰将包括影响分子基态稳定性的空间和电子变化。将使用1H NMR和UV光谱检查结构变化对金属离子结合和非物理性质的影响。