Synthesis and Chemical Biology of Bioactive Natural Products

生物活性天然产物的合成与化学生物学

• 批准号: 10362020
• 负责人: Joshua G. Pierce
• 金额: $ 3.45万
• 依托单位: NORTH CAROLINA STATE UNIVERSITY RALEIGH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-01-01 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10362020
• 关键词: Bacterial Infections; Biology; Chemicals; Complex; Development; Disease; Family; Grant; Guanidines; Lead; Malignant Neoplasms; Microbial Biofilms; Natural Products; Oxazolidinones; Parents; Public Health; Reaction; Research; Source; Students; Synthesis Chemistry; United States National Institutes of Health; Work; analog; antimicrobial; bacterial resistance; bioactive natural products; chemical reaction; clinically relevant; human disease; innovation; interest; natural antimicrobial; novel; novel drug class; programs; therapeutic development; therapeutic lead compound

Project Summary/Abstract This proposal describes our program focused on the development of novel chemical reactions for complex molecule synthesis, innovative strategies for molecule synthesis, and the application of these reactions and strategies to antimicrobial natural products The objective of the proposed research is to develop a scalable and expedient approach to several bioactive natural product families and leverage the synthetic work to develop new chemical probes and lead compounds for therapeutic development. We have developed several programs in this regard over our previous 5 years of NIH support and are excited to expand our efforts while advancing our existing projects to the next level. Of particular interest to date are polycyclic guanidine, oxazolidinone, curvulamines and absyssomicins to explore antimicrobial and/or anti-biofilm activity. We expect that our synthetic work will provide new reactions to construct molecules of broad utility and lead to approaches to natural products that enable their use as chemical probes. These synthetic studies are complimented by in-house chemical biology studies to explore the activity and mechanism of both natural products and analogs against clinically relevant diseases. Taken together, these efforts will provide a framework for the development of new synthetic chemistry and potential lead compounds for the treatment of bacterial infections as well as other diseases as new activity is uncovered.

项目概要/摘要 该提案描述了我们的计划，重点是开发复杂的新型化学反应 分子合成、分子合成的创新策略以及这些反应和的应用 抗菌天然产品策略 拟议研究的目的是开发一种可扩展且便捷的方法来处理几种生物活性物质 天然产品系列并利用合成工作开发新的化学探针和先导化合物 用于治疗开发。在过去的 5 年里，我们在这方面制定了多项计划 NIH 支持并很高兴能够扩大我们的努力，同时将我们现有的项目提升到一个新的水平。的 迄今为止特别值得探索的是多环胍、恶唑烷酮、curvulamines 和 Absyssomicins 抗菌和/或抗生物膜活性。 我们期望我们的合成工作将提供新的反应来构建具有广泛用途和领先地位的分子 能够将天然产物用作化学探针的方法。这些综合研究是 得到内部化学生物学研究的补充，探索天然物质的活性和机制 针对临床相关疾病的产品和类似物。总而言之，这些努力将提供一个框架 开发用于治疗细菌的新合成化学和潜在先导化合物 随着新活动的发现，感染和其他疾病也会发生。