CORE--CHEMISTRY

核心--化学

• 批准号: 7215391
• 负责人: DONALD W LANDRY
• 金额: $ 27.02万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7215391
• 关键词: Acrylamide; Acrylamides; Affinity; Affinity Chromatography; Animals; Binding; Biochemical; Biological; Biological Assay; Chemistry; Class; Core Facility; Equipment; Ion Channel; Label; Organic Synthesis; Parents; Proteins; Radio; Radiolabeled; Range; Structure; Testing; analog; base; crosslink; detector; in vivo; instrumentation; mass spectrometer; radiotracer; response; rottlerin; small molecule; tool

equipment and instrumentation necessary for organic synthesis and small molecule characterization including a Shimadzu LC-Mass spectrometer, a Varian 300-MHz 'H(13C, I5N, 31P)-nmr spectrometer and a Biacore plasmon resonance detector. The small molecules to be synthesized for each project will.be based on known parent compounds with previously demonstrated activity. The parent compounds include JTV-519 for the Marks project, rottlerin for the Marx project, R-L3 and acrylamide derivatives for the Kass project, and JTV ¿derivatives and agents to cross-link and label proteins for the Karlin project. As required for each project, the Core will prepare specific classes of derivatives that will serve as tools to define structure and activity. The range of classes will include tethered analogs for affinity purification, radio-labeled analogs for binding studies, and analogs for photoaffmity labeling that contain a radiolabel or a tether for affinity purification. The Core will also produce selected parent compounds and analogs on a preparative scale for in vivo testing in the Animal Core Facility of the PPG. The ability to tailor molecules in response to biological and biochemical activity provides a potent tool for investigating the allosteric modulation of ion channels. JTV Rottlerin JTV R-L3 Class of Molecule to be prepared: (Marks) (Marx) (Karlin) (Kass) Parent Compound X X X Analogs for Structure-Activity II. Studies X X 3H- Labeled Analogs X IV. Tethered Analogs for Affinity Purification or Biacore Assay X V. Radiolabeled Photoaffinity Analogs X VI. Photoaffinity Analogs Tethered for Affinity Purification X PHS 398/2590 (Rev. 09/04) Page 2~ Continuation Format Page

有机合成和小分子表征所需的设备和仪器，包括 Shimadzu LC-质谱仪、Varian 300-MHz 1H（13 C，15 N，31 P）-nmr光谱仪和Biacore质谱仪。 等离子体共振检测器每个项目要合成的小分子will.be基于已知的 具有先前证实的活性的母体化合物。母体化合物包括JTV-519， Marks项目，马克思项目的罗特勒林，Kass项目的R-L3和丙烯酰胺衍生物，以及JTV 用于Karlin项目的交联和标记蛋白质的衍生物和试剂。根据每个项目的要求， 核心将准备特定类别的衍生工具，这些衍生工具将作为定义结构和活动的工具。的 类别的范围将包括用于亲和纯化的栓系类似物，用于结合研究的放射性标记类似物， 以及用于光亲和标记的类似物，其含有放射性标记或用于亲和纯化的系链。芯会 还以制备规模生产选定的母体化合物和类似物，用于动物体内试验 PPG的核心设施。根据生物和生物化学活动调整分子的能力 为研究离子通道的变构调节提供了有力的工具。 JTV R-L3 分子类别为 准备：（马克思）（马克思）（卡林）（卡斯） 母体化合物X X X 结构-活性类似物 二.研究X X 3 H-标记的类似物X 四. Affinity的系留类似物 纯化或Biacore检测X 诉放射标记 光亲和类似物X 六.光亲和类似物 绑定亲和力 纯化X PHS 398/2590（09/04修订版）第2页~续格式页