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: 10728370
• 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/10728370
• 关键词: Bacterial Infections; Biology; Chemicals; Complex; Development; Disease; Family; Guanidines; Lead; Malignant Neoplasms; Microbial Biofilms; Natural Products; Oxazolidinones; Public Health; Reaction; Research; Source; 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.

项目摘要/摘要 该提案描述了我们的计划，重点是开发复杂的新化学反应 分子合成，分子合成的创新策略以及这些反应的应用和 抗菌天然产品的策略 拟议的研究的目的是开发一种可扩展和方便的方法来进行几种生物活性 天然产品家族并利用合成工作来开发新的化学探针和铅化合物 用于治疗发展。在过去的5年中，我们在这方面开发了多个计划 NIH的支持，并很高兴扩大我们的努力，同时将现有项目提高到一个新的水平。的 迄今为止特别感兴趣的是多环鸟嘌呤，黄唑啉酮，曲曲霉和丙糖蛋白探索 抗菌和/或抗生物膜活性。 我们预计我们的合成工作将为构建广泛效用的分子提供新的反应，并领导 采用能够用作化学探针的天然产品的方法。这些合成研究是 由内部化学生物学研究称赞，以探索两种自然的活性和机制 针对临床相关疾病的产品和类似物。综上所述，这些努力将提供一个框架 为了开发新的合成化学和潜在铅化合物，以治疗细菌 发现了感染以及其他疾病，因为新活动被发现。