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.

本项目旨在确定荧光连接剂技术的商业价值。荧光接头由两个官能团定义，这两个官能团最初是彼此特异性反应以形成荧光键的非荧光化学柄。这些化学把手容易地并入聚合物、小分子、蛋白质、核酸和其他生物分子中。结果是一种允许非破坏性、高灵敏度反应监测的缀合方法，这在筛选反应条件、优化两个分子之间的缀合和确定缀合效率中是必要的。拟议的项目是评估荧光连接技术的价值，该技术提供了一个明确的程序，指导任何对化学知之甚少的研究人员将两个不同的分子连接在一起，然后通过荧光验证连接。该方法不需要对下游应用进行广泛的纯化，在确定缀合效率方面提供更高的灵敏度，并且缩短了在高通量系统中潜在使用的处理时间。连接两个不同的分子在治疗剂和材料开发中具有重要作用。例如，将疾病归巢信号与治疗药物连接可以产生组织特异性递送，以通过降低施用的药物浓度和增加靶向药物递送来避免副作用。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切实可行的办法，以高度敏感的方式监测这些联系。其结果将有可能简化发现过程，提供更有效的药物缀合物用于组织特异性递送，并减少暴露于可能导致医疗和环境损害的有害有机溶剂。