CORE--CHEMISTRY

核心--化学

基本信息

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
项目类别：
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

项目摘要

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 'H(13C、I5N、31P)-nmr 光谱仪和 Biacore 每个项目要合成的小分子将基于已知的。先前已证明具有活性的母体化合物母体化合物包括 JTV-519。 Marks项目、Marx项目的rottlerin、Kass项目的R-L3和丙烯酰胺衍生物以及JTV ¿用于卡林项目交联和标记蛋白质的衍生物和试剂根据每个项目的要求， Core 将准备特定类别的衍生品，作为定义结构和活动的工具。类别范围包括用于亲和纯化的系留类似物、用于结合研究的放射性标记类似物、以及包含用于亲和纯化的放射性标记或系绳的光亲和标记类似物。还以制备规模生产选定的母体化合物和类似物，用于动物体内测试 PPG 的核心设施能够根据生物和生化活性定制分子。为研究离子通道的变构调节提供了有效的工具。 JTV 罗特林 JTV R-L3 分子类别准备：（马克）（马克思）（卡林）（卡斯）母体化合物 X X 结构-活性类似物二、研究 3H-标记类似物 IV. 亲和力的束缚类似物纯化或 Biacore 测定五、放射性标记光亲和类似物 VI. 光亲和类似物因亲和力而束缚纯化 PHS 398/2590 (Rev. 09/04) 第 2 页~ 继续格式页