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为分子库小分子存储库（MLSMR）提供一个包含 10-10 个样本的中试规模库（PSL），扩大分子库探针生产中心网络（MLPCN）可用的化学多样性。每年 25 种新颖或稀有、结构复杂的海洋天然产物。这些化合物将源自 HBOI 冷冻生物保藏库中的海洋大型生物，包括海绵、海鞘、刺胞动物和藻类，重点是从难以接近的深水海洋环境中收集的生物。该项目的主要重点是提供科学结构上新颖的化合物，但除此之外，还将提供 MLSMR 目前无法获得的具有不寻常结构的稀有天然产物。提供的所有化合物均符合 MLSMR 的 10 mg 标准、> 90% 纯度以及在氯仿:甲醇 9:1 或 DMSO 中的溶解度。 HBOI 拥有超过 15,000 种海洋生物的特殊收藏，可用于生成中试规模的图书馆，其中许多生物是 HBOI 收藏所独有的。我们的研究小组最近进行的一个项目是创建一个与高通量筛选兼容的富集组分的“峰库”，该项目在检测过去未曾进行过化学研究的生物体中的异常化学型方面取得了巨大成功。峰库中的大多数馏分仅需要一个额外的纯化步骤即可提供纯材料，并且初始分馏（中压液相色谱）的规模可以轻松分离大量材料。我们最近扩展了 HBOI 筛选平台，并观察到 ​​Peak 库中发现的许多新化学型会影响独特的生物靶标，并代表新的先导结构和用于研究生物过程的优秀探针。我们将在用于生成峰库的方法的基础上，创建一个独特的中试规模的纯不寻常天然产物库，扩大 MLSMR 目前可用的化学多样性空间。 公共健康相关性：拟议的研究项目将为分子图书馆小分子存储库提供一个独特的中试规模的新型稀有天然产物库，并扩大该库的化学多样性。这将增加分子路线图实现其目标的机会，即发现生物机制的新探针以及与人类健康相关的具有独特生物活性的化合物。