Core E Haggie Bioassays Core

项目摘要(见说明)：合成核心为囊性纤维化研究和翻译核心中心提供重要的使能技术。合成核心(核心D)拥有这项工作所需的所有设备，合成核心总监Kurth教授拥有在靶向和库小分子合成中管理和实施该设备的丰富经验。综合核心与研究基地的项目进行互动，提供三个级别的服务。一级--合成核心服务的最高级别--包括合成核心集中参与通过详尽的合成优化和探索结构-活性关系(SAR)。我们预计，AF508-CFTR校正器/电位器以及CACC/TMEM16A激活剂的这种参与程度将继续下去。根据高通量筛选(HTS)核心(核心A)的发现进度以及重点化学在满足计划目标方面的重要性，其他项目也可能需要这种程度的参与。11级-第二级合成核心参与-涉及先导化合物的重新合成、提供药物化学建议和SAR分析。许多项目将从这一级别的综合核心服务中受益。第111级--第三级服务--只需要最少的合成核心工作，包括为项目研究提供已经合成的化合物，以及提供关于活性化合物的药物化学的建议。虽然单个项目的需求将推动合成核心的大部分活动，但核心也将与A/B/C/E核心互动--主要是提供其工作所需的任何单独化合物。合成核心将与HTS核心密切互动，以验证HIT的身份，并通过HIT重新合成和光谱表征来验证HIT的活性。所有由项目和核心活动合成核心提供的先导化合物都将得到高度提纯(一般为-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%).