NMR spectroscopy instrumentation for probing intermolecular interations

用于探测分子间相互作用的核磁共振波谱仪器

• 批准号: 7125669
• 负责人: Maurizio Pellecchia
• 金额: $ 144.48万
• 依托单位: SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2008-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7125669
• 关键词: Affinity; Area; Automation; Biology; Chemicals; Chemistry; Communicable Diseases; Communities; Complex; Dimensions; Early identification; Funding; Genomics; Label; Laboratories; Lead; Liquid substance; Macromolecular Complexes; Malignant Neoplasms; Monitor; NMR Spectroscopy; Noise; Nucleic Acids; Numbers; Process; Proteins; Research; Resolution; Roentgen Rays; Role; Sampling; Signal Pathway; Signal Transduction; Site; Solutions; Structure; Techniques; base; design; drug discovery; instrument; instrumentation; intermolecular interaction; pathogen; small molecule; structural biology

DESCRIPTION (provided by applicant): Nuclear magnetic resonance spectroscopy instrumentation for probing intermolecular interactions Nuclear magnetic resonance spectroscopy in solution has evolved into a powerful technique for structure determination of proteins and nucleic acids. More recently, a number of NMR-based approaches have been developed to monitor and characterize intermolecular interactions. These approaches offer unique advantages over other techniques and find their utility in structural biology, chemical biology and even drug discovery. The use of differential labeling and the advent of TROSY-type techniques have provided an additional dimension to the use of NMR in the structural biology field in the identification and characterization of macromolecular interfaces. Moreover, NMR has also found an important role in the study and characterization of the interactions between small organic molecules and macromolecular targets, particularly useful in lead identification and optimization processes. We have recently successfully employed these techniques to characterize intermolecular interfaces and to subsequently guide the design of high affinity small molecule binders. At the interface between chemistry and biology, these applications of solution NMR spectroscopy allow early identification of key interaction sites between macromolecular complexes therefore providing rapid information on possible targeting sites in absence of atomic resolution X- ray structures of the complex. Expanding on our current unique capabilities and expertise in these areas of research, we request funds for a 700 MHz instrument equipped with accessories for a higher signal-to-noise ratio (cryoprobe) and laboratory automation (liquid handler and sample changer). The requested instrument will serve in part our San Diego Chemical Genomics Center, so that it would be available to the entire scientific community, and will also support three major multi- component projects in the areas of cell signaling pathways in cancer and host-pathogen interactions in infectious diseases.

描述（由申请人提供）：用于探测分子间相互作用的核磁共振波谱仪器溶液中的核磁共振波谱已经发展成为一种测定蛋白质和核酸结构的强大技术。最近，一些基于核磁共振的方法被开发出来监测和表征分子间相互作用。与其他技术相比，这些方法具有独特的优势，在结构生物学、化学生物学甚至药物发现方面都有应用。微分标记的使用和trosy型技术的出现为结构生物学领域中大分子界面的识别和表征提供了核磁共振的额外维度。此外，核磁共振在有机小分子与大分子靶标之间相互作用的研究和表征中也发挥了重要作用，特别是在铅的鉴定和优化过程中。我们最近成功地利用这些技术来表征分子间界面，并随后指导高亲和力小分子粘合剂的设计。在化学和生物学之间的界面，溶液核磁共振波谱的这些应用允许早期识别大分子复合物之间的关键相互作用位点，因此在没有原子分辨率X射线结构的情况下提供可能的靶向位点的快速信息。扩展我们目前在这些研究领域的独特能力和专业知识，我们要求为配备更高信噪比（冷冻探头）和实验室自动化（液体处理器和样品转换器）配件的700 MHz仪器提供资金。所要求的仪器将部分服务于我们的圣地亚哥化学基因组学中心，以便整个科学界都可以使用，并且还将支持癌症细胞信号传导途径和传染病宿主-病原体相互作用领域的三个主要多组分项目。