Rapid Screening and Dereplication of Marine Symbiotic Natural Products

海洋共生天然产物的快速筛选和去复制

• 批准号: 7845758
• 负责人: Eric W Schmidt
• 金额: $ 38.64万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-15 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7845758
• 关键词: Actinobacteria class; Actinomyces; Animals; Area; Arts; Bacteria; Biological; Biological Factors; Chemicals; Chemistry; Clinical; Collaborations; Communities; Data; Data Set; Databases; Development; Equipment; Florida; Goals; Health; Human; Individual; Island; Knowledge; Libraries; Link; Location; Marines; Mass Spectrum Analysis; Methods; Outcome; Pharmacologic Substance; Prevalence; Procedures; Process; Property; Protocols documentation; Publications; Research Personnel; Role; Science; Screening procedure; Soil; Source; Speed; Structure; Symbiosis; Techniques; Technology; Therapeutic; United States; United States National Institutes of Health; Universities; Utah; Water; Wisconsin; ascidian; design; drug discovery; experience; high throughput screening; interest; marine natural product; marine organism; novel; novel therapeutics; public health relevance; rapid technique; scaffold; small molecule; tool

DESCRIPTION (provided by applicant): The majority of pharmaceuticals are derived from natural products either directly or indirectly. However, the pipeline to new natural products has been drying up over the last decades as the technologies became less amenable to high- throughput screening and as finding new natural products became increasingly difficult. Substantial progress has been made in these areas by numerous labs, but there are still gaps in technology and in basic understanding of natural product sources. In this project, we will provide new methods and data to help fill these remaining gaps. In addition, we will build natural product compound libraries for screening at NIH and at the University of Wisconsin. The new methods include more rapid, automated, and integrated techniques for extraction, purification, and dereplication of natural products. Basic studies of natural product sources using marine symbiotic bacteria are aimed at answering questions about the most fruitful places to find new natural product producers and about methods to obtain these promising bacteria. These biological and chemical studies are synergistic and will provide the first large, ordered set of data linking cultivated symbiotic bacteria to chemistry in whole animals. The resulting methods are designed to be widely useful in multiple labs and to help in the development of broadly shared platforms for dereplication. The resulting libraries of natural products will be used in a variety of screens at established, high-throughput centers at NIH and U. Wisconsin. We will pursue promising leads as potential new pharmaceuticals. PUBLIC HEALTH RELEVANCE: We will develop new methods for the rapid discovery of bioactive natural products and provide new data about sources of natural products that enable drug discovery. We will also provide libraries of natural products for screening. These results will have a large impact on natural products sciences because of new methods and knowledge. The human health impact will result from these new methods and potentially from new therapeutic small molecules discovered in the course of the project.

描述（由申请人提供）：大多数药物是直接或间接衍生自天然产品的。但是，在过去的几十年中，随着技术变得不太适合高吞吐量筛查，新天然产品的管道一直在干燥，并且发现新的天然产品变得越来越困难。许多实验室在这些领域取得了重大进展，但是技术和对自然产品来源的基本了解仍然存在差距。在此项目中，我们将提供新的方法和数据，以帮助填补这些剩余的空白。此外，我们还将在NIH和威斯康星大学建造自然产品复合图书馆。这些新方法包括更快，自动化和集成技术，用于提取，纯化和自然产物的消除。使用海洋共生细菌对天然产品来源的基础研究旨在回答有关找到新的天然产品生产者的最富有成果的问题，以及有关获得这些有希望的细菌的方法。这些生物学和化学研究是协同作用的，将提供第一组有序的数据集，该数据将培养的共生细菌与整个动物的化学联系联系起来。所得的方法旨在在多个实验室中广泛有用，并帮助开发广泛共享的平台以进行删除。最终的天然产品库将用于NIH和U. Wisconsin建立的高通量中心的各种屏幕。我们将作为潜在的新药物追求有希望的潜在客户。 公共卫生相关性：我们将开发新的方法来快速发现生物活性天然产品，并提供有关启用药物发现的天然产品来源的新数据。我们还将提供天然产品库供筛查。由于新方法和知识，这些结果将对天然产品科学产生很大的影响。人类健康的影响将源于这些新方法，并有可能是由于项目过程中发现的新的治疗性小分子而产生的。