Lanthanide Binding Tags: New Chemical Tools for Proteomics

麻省理工学院化学系的Barbara A. Imperiali、波士顿大学医学院生理与生物物理系的Karen Allen和德国法兰克福歌德大学化学系的Harald Schwalbe获得了化学合作研究项目的奖励，该项目由化学系、分子与细胞生物学系和多学科活动办公室提供资金支持。该团队将开展研究，旨在为结构和功能蛋白质组学提供一种新颖且普遍适用的化学工具。镧系结合标签（lbt）由短肽序列（少于25个氨基酸）组成，可以结合三价镧系离子，可以结合到蛋白质中，用于发光光谱，核磁共振和x射线分析，这些应用依赖于结合复合物的独特光物理性质。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，包括组合合成和简单蛋白质支架的定向设计。这些序列将被整合到目标蛋白中，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合作测试。镧系元素结合标签策略提供了一种单一的工具，一种化学标签，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，这些都需要克服蛋白质组学的挑战。该项目的目标是提供LBT技术的一种形式，可以很容易地由化学、生物和生物医学领域的各种终端用户实施。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，包括蛋白质组学研究前沿的国际合作。

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.