Chemical Synthesis and High-Throughput Analytics Shared Resource

CORE 005-化学合成和高通量分析共享 资源 项目摘要/摘要 范德比尔特化学合成和高通量分析共享资源(CSHTASR)提供 范德比尔特-英格拉姆癌症中心(VICC)研究社区的最先进能力，包括 我们在梅哈里医学院、田纳西州立大学和其他NCI癌症中心的VICC成员和合作伙伴 中锋。CSHTASR致力于利用化学和分析技术的力量来支持研究 需要应用或发现化学工具来回答生物问题。此项目支持的项目 共享资源包括： ·药物化学；包括Hit优化和Hit-to-Lead活动，以及发现新的 用于临床前或假说驱动的体外研究的化合物 ·大规模合成(10-100克)和化合物配方，以支持活体动物研究 ·合成包括代谢物在内的同位素标记化合物，用于#年的质谱定量 临床标本 ·亲和和荧光探针的合成和设计 ·合成天然和非天然核苷酸和多肽 ·高通量仪器，可为多种分析提供静态和动态读数，包括 生化、基于细胞、表型、基于图像的高含量、3D培养模型和整体 生物体 ·功能基因组筛选，以确定新的药物靶点和药物作用/耐药的机制(S) ·支持复杂动态模型的动力学分析 ·“有重点的”化合物/药物库筛选和药物组合--例如，食品和药物管理局的药物收藏(1300)， 翻译项目的抗癌套装(&gt；1,000)等 ·对不同的大型(350,000)化合物文库进行全面的高通量筛选活动，这是 与药物化学协同，发现治疗疾病的新化学和新化合物- 相关目标。 CSHTASR通过仪器技术和员工专业知识的结合来提供这些服务。 机构和美国国立卫生研究院的资金已经投入，以获得有效实施 和高效的CSHTASR服务。此外，我们的大院和FGS图书馆是宝贵的材料资源 允许询问生物活动，提供对目标/途径识别和起点的洞察 用于化学探针的优化。CSHTASR雇佣了训练有素的领导层和支持人员， 在先进的化学技术和高温超导方法方面拥有丰富的经验和专业知识。

CORE 005 – CHEMICAL SYNTHESIS AND HIGH-THROUGHPUT ANALYTICS SHARED RESOURCE PROJECT SUMMARY/ABSTRACT The Vanderbilt Chemical Synthesis and High-throughput Analytics Shared Resource (CSHTASR) provides state-of-the-art capabilities for the Vanderbilt-Ingram Cancer Center (VICC) research community, inclusive of our VICC members and partners at Meharry Medical College, Tennessee State University, and other NCI Cancer Centers. CSHTASR works to harness the power of chemistry and assay technologies to support research requiring the application or discovery of chemical tools to answer biological questions. Projects supported by this shared resource include: • Medicinal chemistry; including hit optimization and hit-to-lead activities, as well as discovery of novel compounds for pre-clinical or hypothesis-driven in vitro studies • Large-scale synthesis (10-100 grams) and compound formulation to support in vivo animal studies • Synthesis of isotopically labeled compounds including metabolites for mass spectral quantification in clinical samples • Synthesis and design of affinity and fluorescent probes • Synthesis of natural and unnatural nucleotides and peptides • High-throughput instrumentation that provides static and kinetic readouts for multiple assays including biochemical, cell-based, phenotypic, high-content image-based, 3D culture models, and whole organisms • Functional genomic screens to identify novel drug targets and mechanism(s) of drug action/resistance • Kinetic assays to support complex dynamic models • “Focused” compound/drug library screening and drug combinations – e.g., FDA drug collection (1,300), anti-cancer set (>1,000), etc., for translational projects • Full high-throughput screening campaigns of diverse, large (>350,000) compound libraries, which is coordinated with medicinal chemistry to discover new chemistry and novel compounds for disease- related targets. The CSHTASR provides these services through a combination of instrument technology and staff expertise. Institutional and NIH funds have been invested to acquire leading-edge instrumentation required for effective and efficient CSHTASR services. In addition, our compound and FGS libraries are valuable material resources that allow interrogation of biological activity, providing insight into target/pathway identification and starting points for chemical probe optimization. The CSHTASR employs a highly trained leadership and support staff with extensive experience and expertise in advanced chemistry techniques and HTS methodologies.