CORE--CHEMISTRY

有机合成和小分子表征所需的设备和仪器，包括 岛津LC-质谱仪、瓦里安300-MHz‘H(13C，I5N，31P)-核磁共振谱仪和Biacore 等离子体共振探测器。为每个项目合成的小分子将基于已知的 具有先前证明的活性的母体化合物。母体化合物包括JTV-519 MARS项目，MARX项目的ROTTERIN，KASS项目的R-L3和丙烯酰胺衍生物，以及JTV ？用于为卡林项目的蛋白质进行交联和标记的衍生物和试剂。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。这个 一系列类别将包括用于亲和纯化的拴系类似物，用于结合研究的放射性标记类似物， 以及含有用于亲和纯化的放射性标记或系绳的光亲和标记的类似物。核心意志 还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。根据生物和生化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中的JTV Rottlerin 分子的类别为 准备：(马克)(马克思)(卡林)(卡斯) 母化合物X X X 结构活性类似物 二、研究 ~3H标记类似物X IV.用于亲和力的系留类比 纯化或Biacore化验X V.无线电标记 光亲和类似物X VI.光亲和性类似物 为亲和力而系绳 净化X PHS 398/2590(09/04版)第2页~续格式页

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