Lanthanide Binding Tags: New Chemical Tools for Proteomics

镧系元素结合标签：蛋白质组学的新化学工具

• 批准号: 0304832
• 负责人: Barbara Imperiali
• 金额: --
• 依托单位: Massachusetts Institute of Technology
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-15 至 2008-10-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0304832&HistoricalAwards=false
• 关键词: Lanthanide; Binding; Tags; New; Chemical

Barbara A. Imperiali, Department of Chemistry, MIT, Karen Allen, Department of Physiology and Biophysics, Boston University School of Medicine and Harald Schwalbe, Department of Chemistry, Goethe University of Frankfurt, Germany, are supported with an award from the Collaborative Research in Chemistry Program with funds provided by the Division of Chemistry, the Division of Molecular and Cellular Biology and the Office of Multidisciplinary Activities. The team will carry out research aimed at producing a novel and generally applicable chemical tool for structural and functional proteomics. Lanthanide binding tags (LBTs), comprised of short peptide sequences (fewer than 25 amino acids) that are optimized to bind trivalent lanthanide ions, can be incorporated into a protein for applications in luminescence spectroscopy, NMR and X-ray analysis that rely upon the unique photophysical properties of the bound complex. These will supersede the capacity of a variety of existing tools in a single entity. LBT sequences will be evolved in the Imperiali lab at MIT through state-of-the-art strategies that include both combinatorial synthesis and directed design stating from simple protein scaffolds. These sequences will be integrated into target proteins and tested by a multidisciplinary, collaborative effort by experts in nuclear magnetic resonance, X-ray crystallography, fluorescence spectroscopy and cell biology. The lanthanide binding tag strategy provides a single tool, a chemical tag, that encompasses the breadth of applications, including nuclear magnetic resonance, X-ray crystallography, and fluorescence spectroscopy and cell biology, needed to conquer the proteome challenge. The goal of the program is to provide the LBT technology in a form that can be readily implemented by a diverse set of end users in the chemical, biological and biomedical communities. Additionally, postdoctoral research scientists, graduate students and undergraduates will be involved in multidisciplinary, multi-institution research that includes an international collaboration at the forefront of proteomics research.

芭芭拉A.麻省理工学院化学系的Imperiali、波士顿大学医学院生理学和生物物理学系的Karen艾伦和德国法兰克福歌德大学化学系的Harald Schwalbe获得了化学项目合作研究奖的支持，该项目的资金由化学系、分子和细胞生物学系以及多学科活动办公室提供。 该团队将开展研究，旨在为结构和功能蛋白质组学生产一种新颖且普遍适用的化学工具。镧系元素结合标签（LBT）由优化为结合三价镧系元素离子的短肽序列（少于25个氨基酸）组成，可以掺入蛋白质中用于依赖于结合复合物的独特生物物理性质的发光光谱、NMR和X射线分析。 这些将取代单一实体中各种现有工具的能力。LBT序列将在麻省理工学院的Imperiali实验室通过最先进的策略进行进化，这些策略包括组合合成和从简单蛋白质支架开始的定向设计。 这些序列将被整合到靶蛋白中，并由核磁共振、X射线晶体学、荧光光谱学和细胞生物学专家进行多学科的合作测试。 镧系元素结合标签策略提供了一个单一的工具，一个化学标签，它涵盖了广泛的应用，包括核磁共振，X射线晶体学，荧光光谱和细胞生物学，需要克服蛋白质组的挑战。 该计划的目标是提供LBT技术，其形式可以由化学，生物和生物医学社区的各种最终用户轻松实施。 此外，博士后研究科学家，研究生和本科生将参与多学科，多机构的研究，其中包括在蛋白质组学研究的最前沿的国际合作。