Core E Haggie Bioassays Core

项目总结（见说明）：合成核心为囊性纤维化研究和转化核心中心提供了重要的使能技术。合成核心（核心D）拥有这项工作所需的所有设备，合成核心主任Kurth教授在靶向和文库小分子合成中管理和实施该设备方面拥有丰富的经验。综合核心与研究基地的项目互动，提供三个层次的服务。一级-合成核心服务的最高级别-由合成核心通过穷举合成集中参与先导化合物优化和结构-活性关系（SAR）探索。我们预计，对于AF 508-CFTR校正剂/增效剂以及CaCC/TMEM 16 A活化剂，这种参与水平将继续。根据高通量筛选（HTS）核心（核心A）的发现进展以及重点化学在实现计划目标方面的重要性，这种参与程度也可能适用于其他项目。II级-合成核心参与的第二级-涉及先导化合物的再合成，提供药物化学建议和SAR分析。许多项目将受益于这一级别的综合核心服务。111级-服务的第三级-需要最小的合成核心工作，包括提供已经合成的化合物用于项目研究，以及提供有关活性化合物的药物化学的建议。虽然个别项目需求将推动合成核心的大部分活动，但核心也将与核心A/B/C/E互动-主要是提供其工作所需的任何个别化合物。合成核心将与HTS核心密切互动，以验证命中的身份，并通过命中再合成和光谱表征验证命中活性。由合成中心为项目和核心活动提供的所有先导化合物都将是高度纯化的（通常为~ 95%）。

PROJECT SUMMARY (See instructions): The Synthesis Core provides vital enabling technology for the Cystic Fibrosis Research and Translational Core Center. The Synthesis Core (Core D) has all of the equipment required for this effort and Prof. Kurth, the director of the Synthesis Core, has broad experience managing and implementing this equipment in targeted and library small molecule synthesis. The Synthesis Core interacts with Projects in the research base, providing three levels of service. Level I - the highest level of Synthesis Core service - constitutes concentrated involvement by the Synthesis Core in lead optimization and exploration of structure-activity relationships (SAR) by exhaustive synthesis. We anticipate that this level of involvement will continue for AF508-CFTR correctors / potentiators as well as for CaCC/TMEM16A activators. Depending on High- Throughput Screening (HTS) Core (Core A) discovery progress as well as the importance of focused chemistry in meeting Program goals, this level of involvement may also be warranted for other Projects. Level ll - the second level of Synthesis Core involvement - involves the resynthesis of lead compounds, provision of medicinal chemistry advice, and SAR analysis. Many Projects will benefit from this level of Synthesis Core service. Level 111 - the third level of service - requires minimal Synthesis Core effort and consists of providing compounds that have already been synthesized for Project studies as well as providing advice on the medicinal chemistry of active compounds. While individual Project needs will drive most of the Synthesis Core's activities, the Core will also interact with Cores A/B/C/E - primarily in providing any individual compounds needed for their work. The Synthesis Core will interact closely with the HTS Core to verify the identity of hits and validate hit activity by hit re-synthesis and spectroscopic characterization. All lead compounds supplied by the Synthesis Core for Project and Core activities will be highly purified (generally at -95%).