Creation of a Marine Natural Products Library to Enhance Life Science Research

创建海洋天然产物库以加强生命科学研究

• 批准号: 7934694
• 负责人: AMY Elizabeth WRIGHT
• 金额: $ 58.07万
• 依托单位: FLORIDA ATLANTIC UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2012-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7934694
• 关键词: Advertising; Agreement; Alzheimer' s Disease; Anti-Bacterial Agents; Antimalarials; Antineoplastic Agents; Automation; Biochemical; Biological; Biological Factors; Biological Sciences; Chemicals; Collaborations; Collection; Communicable Diseases; Communities; Companions; Contracts; Databases; Diabetes Mellitus; Disease; Diversity Library; Equipment; Fractionation; Freezing; Funding; Generations; Goals; High Pressure Liquid Chromatography; Histone Deacetylase Inhibitor; Human; I Kappa B-Alpha; Industry; Institutes; Laboratories; Lead; Libraries; Liquid Chromatography; Liquid substance; Malaria; Malignant Neoplasms; Manufacturer Name; Marines; Measurable; Medicine; Methods; Natural Products Chemistry; Nature; Occupations; Organism; Outcome; Pharmaceutical Preparations; Process; Production; Proteome; Research; Research Infrastructure; Research Project Grants; Research Support; Resources; Robotics; Screening procedure; Source; Specimen; Stream; Structure; Students; System; Therapeutic Agents; Training; Water; data mining; drug development; drug discovery; follow-up; graduate student; high school; high throughput screening; inhibitor/antagonist; marine natural product; marine organism; material transfer agreement; meetings; microbial; novel; novel therapeutics; postdoctoral investigator; pressure; programs; public health relevance; repository; scaffold; small molecule libraries; tool; web page

DESCRIPTION (provided by applicant): Natural products represent an excellent source of novel chemical scaffolds that are inherently biologically active. It has been estimated that 78% of the 90 antibacterial agents and 62% of the 79 anticancer agents approved for use in the US over the past two decades have their origins in natural products. With advances in robotics, High Throughput Screening (HTS) has become the primary approach used worldwide to discover new lead compounds for drug development and chemical probes to better understand the disease process. Unfortunately, natural products extracts are not readily amenable for use in discovery programs that use HTS which has led to a significant reduction in opportunities for new drug and chemical probe discovery. The current proposal seeks to overcome this obstacle by creating a unique library of marine natural products (both enriched fractions and purified compounds) that is compatible with HTS and is available to the Life Sciences Research Community as a new research tool. In this two year project we seek to create a unique library of marine natural products, designated as the Harbor Branch Oceanographic Institute (HBOI) Marine Natural Product Library (MNPL), which will serve as a long term resource to the scientific community. HBOI has been engaged in the production of such a library for the past five years as part of a National Cooperative Drug Discovery Project and has successfully created a library from approximately 150 organisms. Screening of the existing chemical library has allowed for the rapid discovery of many new structures including novel histone deacetylase inhibitors, MCL-1 inhibitors, anti-malarial agents and inhibitors of nuclear factor kappa B. HBOI has a repository of over 14,000 frozen marine specimens and 19,000 marine microbial isolates that could be used in generation of an expanded Marine Natural Products Library. In the current proposal we seek to greatly expand the diversity of the library through adding automation to the fractionation process and hiring new graduates and students to conduct chemical fractionation on 750-1250 organisms found in the HBOI Frozen Organism Repository and 250-350 organisms from the Marine Microbial Culture Collection. The library will be made available to external collaborators through material transfer agreements, collaborative research agreements and sponsored research projects. Public Health Relevance: This project will create a unique resource - the HBOI Marine Natural Products Library- for the discovery of biological probes and new medicines. This resource will be a library of pure and enriched fractions derived from marine organisms that will be available for screening by the High Through put Screening Community. Such a library will provide access to unique chemical diversity to enhance the US Life Science Research Enterprise.

描述（由申请人提供）：天然产品代表了固有生物学活性的新型化学支架的极好来源。据估计，在过去的二十年中，在美国批准使用的90种抗菌剂中有78％和79名抗癌药物中有62％起源于天然产物。随着机器人技术的进步，高吞吐量筛查（HTS）已成为全球使用的主要方法，以发现药物开发的新铅化合物和化学探针，以更好地了解疾病过程。不幸的是，天然产品提取物不容易用于使用HTS的发现计划，这些HTS导致新药和化学探针发现的机会大大减少。当前的建议旨在通过与HTS兼容的独特海洋天然产品（富集的分数和纯化化合物）来克服这一障碍，并可以作为新的研究社区作为一种新的研究工具。在这个为期两年的项目中，我们试图创建一个独特的海洋天然产品库，该图书馆被指定为港口分支海洋学研究所（HBOI）海洋天然产品图书馆（MNPL），该图书馆将作为科学界的长期资源。在过去的五年中，HBOI一直从事这样一个图书馆的生产，这是国家合作毒品发现项目的一部分，并成功地创建了大约150个生物体的图书馆。对现有化学库的筛选允许快速发现许多新结构，包括新型组蛋白脱乙酰基酶抑制剂，MCL-1抑制剂，抗疟疾剂和核因子Kappa B. Hboi的抑制剂Kappa B. Hboi具有超过14,000个冷冻海洋标本的存储库，并具有19,000海洋隔离剂，可以在生成一代人的生成中使用19,000个海洋隔离材料。在当前的建议中，我们试图通过将自动化为分馏过程增加自动化，并雇用新的毕业生和学生在HBOI冷冻生物储存库中发现的750-1250生物体和250-350生物体中的有机体中的750-1250生物体进行化学分馏，从而大大扩展图书馆的多样性。图书馆将通过物质转移协议，协作研究协议和赞助研究项目提供给外部合作者。 公共卫生相关性：该项目将创建独特的资源 - HBOI海洋天然产品库 - 用于发现生物探针和新药物。该资源将是一个由海洋生物衍生而成的纯净和丰富分数的库，这些库将通过PUT筛查社区进行筛查。这样的图书馆将提供独特的化学多样性，以增强美国生命科学研究企业。