I-Corps: Easy to use clickable linker technology

I-Corps：易于使用的可点击链接器技术

• 批准号: 1242237
• 负责人: Qian Wang
• 金额: $ 5万
• 依托单位: University South Carolina Research Foundation
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1242237&HistoricalAwards=false
• 关键词: Corps; Easy; use; clickable; linker

This project is to determine the commercial value of the fluorogenic linker technology. The fluorogenic linker is defined by two functional groups that are initially non-fluorogenic chemical handles which specifically react with each other to form a fluorescent linkage. These chemical handles are readily incorporated in polymers, small molecules, proteins, nucleic acids, and other biomolecules. The result is a conjugation approach that allows for non-destructive, highly sensitive reaction monitoring, which will be necessary in screening reaction conditions, optimizing conjugations between two molecules, and determining conjugation efficiencies. The proposed project is to assess the value of a fluorogenic linker technology that provides a well defined procedure that guides any researcher with little knowledge in chemistry to link two different molecules together, and then verify the linkage through fluorescence. The procedure will not require extensive purification for downstream applications, provide higher sensitivity in determining conjugation efficiency, and shorten processing time for potential use in high throughput systems.Linking two different molecules has a significant role in development of therapeutic agents and materials development. For instance, linking a disease homing signal and a therapeutic drug can yield tissue specific delivery to avoid side-effects by reducing administered drug concentrations, and increasing targeted drug delivery. Such uses are common for many biopharmaceutical and biotech companies that rely on developing new protein-based therapeutics. The proposed project provides a practical approach to monitor these linkages in a highly sensitive manner. The result will have the potential to streamline discovery process, provide more effective drug conjugates for tissue specific delivery, and reduce exposure to harmful organic solvents that can cause both medical and environmental damages.

本项目是为了确定荧光连接物技术的商业价值。所述荧光连接物由两个官能团限定，所述两个官能团最初是非荧光化学手柄，它们相互特异性地反应以形成荧光键。这些化学手柄很容易结合到聚合物、小分子、蛋白质、核酸和其他生物分子中。其结果是一种允许非破坏性、高灵敏度的反应监测的偶联方法，这将是筛选反应条件、优化两个分子之间的偶联以及确定偶联效率所必需的。拟议的项目是评估荧光连接物技术的价值，该技术提供了一种定义明确的程序，指导任何缺乏化学知识的研究人员将两个不同的分子连接在一起，然后通过荧光验证这种联系。该过程不需要对下游应用进行广泛的纯化，在确定偶联效率方面提供了更高的灵敏度，并缩短了处理时间，潜在地用于高通量系统。连接两个不同的分子在治疗药物和材料开发中具有重要作用。例如，将疾病定位信号与治疗药物联系起来，可以产生组织特异性传递，通过降低给药浓度和增加靶向药物传递来避免副作用。这种用途对于许多依赖于开发新的基于蛋白质的疗法的生物制药和生物技术公司来说是常见的。拟议的项目提供了一种以高度敏感的方式监测这些联系的实际办法。这一结果将有可能简化发现过程，为组织特异性给药提供更有效的药物结合物，并减少对可能导致医疗和环境损害的有害有机溶剂的暴露。