Production of Pilot Scale Libraries of Marine Natural Products

海洋天然产物中试规模库的生产

• 批准号: 8247697
• 负责人: AMY Elizabeth WRIGHT
• 金额: $ 35.22万
• 依托单位: FLORIDA ATLANTIC UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-05 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8247697
• 关键词: Affect; Algae; Biological; Biological Factors; Biological Process; Chemicals; Chloroform; Cnidaria; Collection; Complex; Dimethyl Sulfoxide; Diversity Library; Environment; Fractionation; Freezing; Generations; Goals; Health; Human; Lead; Libraries; Liquid Chromatography; Marines; Methanol; Methods; Molecular; Molecular Bank; Organism; Porifera; Production; Relative (related person); Research; Research Project Grants; Science; Screening procedure; Solubility; Structure; Water; ascidian; high throughput screening; marine natural product; marine organism; meetings; novel; pressure; public health relevance; repository; small molecule

DESCRIPTION (provided by applicant): The goal of this project is expand the chemical diversity available to the Molecular Library Probe Production Center Network (MLPCN) by providing the Molecular Libraries Small-Molecule Repository (MLSMR) a pilotscale library (PSL) of 10-25, novel or rare, structurally complex marine natural products per year. The compounds will be derived from marine macro-organisms in the HBOI Frozen Organism Repository including sponges, ascidians, cnidarians, and algae with an emphasis on organisms collected from less accessible deep-water marine environments. The primary focus of the project will be to provide compounds that are structurally new to science but in addition to these, rare natural products with unusual structures that are not currently available to the MLSMR will also be provided. All compounds provided will meet the MLSMR's criteria of 10 mg, > 90% purity and solubility in either chloroform:methanol 9:1 or DMSO. HBOI has an exceptional collection of over 15,000 marine organisms that can be used in generation of the pilot-scale library with many of the organisms being unique to the HBOI collection. A recent project conducted by our research group to create a "Peak Library" of enriched fractions compatible with high throughput screening, has been highly successful in detecting unusual chemotypes in organisms which had not been chemically investigated in the past. The majority of the fractions in the Peak Library require only one additional purification step to provide pure materials and the scale of the initial fractionation (medium pressure liquid chromatography) leads readily to the isolation of larger quantities of materials. We have recently expanded the HBOI screening platform and have observed that many of the novel chemotypes found in the Peak Library affect unique biological targets and represent novel lead structures and excellent probes for studying biological processes. We will build upon the methods used to produce our Peak Library to create a unique pilot scale library of pure unusual natural products that expands the chemical diversity space currently available in the MLSMR. PUBLIC HEALTH RELEVANCE: The proposed research project will provide a unique pilot scale library of new and rare natural products to the Molecular Libraries Small Molecule Repository and expand the chemical diversity of the library. This will enhance the Molecular Roadmap's opportunities for meeting their goal of discovering new probes of biological mechanisms as well as compounds with unique biological activities relative to human health.

描述（由申请人提供）：该项目的目标是通过提供分子图书馆（MLSMR）的分子图书馆（MLSMR）的PILOTSCALE图书馆（PSL）10-25的10-25，新颖或稀有的结构复杂的海上天然产物，每年扩大分子库探针生产中心网络（MLPCN）可用的化学多样性。这些化合物将源自HBOI冷冻生物存储库中的海洋宏观有机体，包括海绵，海藻，Cnidarians和藻类，重点是从易于获取的深水海洋环境中收集的生物体。该项目的主要重点是提供科学结构上新的化合物，但除这些罕见的天然产品外，还将提供MLSMR目前无法使用的异常结构。所提供的所有化合物将符合MLSMR的标准10 mg，纯度> 90％且溶解度在氯仿：甲醇9：1或DMSO中。 HBOI拥有超过15,000种海洋生物的特殊收藏，可用于生成飞行员规模的图书馆，许多生物是HBOI收藏品所特有的。我们的研究小组最近进行的一个项目，旨在创建与高吞吐量筛选兼容的富集级分的“峰值库”，在检测过去尚未化学研究的生物体中的异常化学型方面非常成功。峰值文库中的大多数分数仅需要一个额外的纯化步骤，即可提供纯材料，而初始分馏（中压液相色谱）的规模很容易导致隔离大量材料。我们最近扩展了HBOI筛选平台，并观察到峰文库中发现的许多新型化学型会影响独特的生物学靶标，并代表了新的铅结构和出色的研究生物学过程的探针。我们将基于用于生产峰值库来创建纯粹不寻常天然产品的独特飞行量表库的方法，该库扩大了MLSMR当前可用的化学多样性空间。 公共卫生相关性：拟议的研究项目将为分子图书馆提供独特的新型和稀有天然产品的试点库库，并扩大图书馆的化学多样性。这将增强分子路线图的机会，以实现其发现新的生物学机制探针以及相对于人类健康的独特生物活动的化合物。