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Development of Natural Product-Inspired Ubiquinone Mimics as Next Generation Agrochemicals

开发受天然产物启发的泛醌模拟物作为下一代农用化学品

基本信息

批准号：
2003692
负责人：
William Wuest
金额：
$ 42.9万
依托单位：
Emory University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2020
资助国家：
美国
起止时间：
2020-06-01 至 2023-05-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=2003692&HistoricalAwards=false
关键词：
Development Natural Product Inspired Ubiquinone

项目摘要

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. William Wuest from Emory University to investigate antifungal natural products active against blight. Blight is broadly defined as the disease or injury of plants marked by the formation of lesions, withering, or death of parts. Effects can range from widespread shortage of a specific crop to complete famine resulting in significant financial burden and societal hardships. In an effort to limit these potential threats, work presented in this research uses chemistry to make antifungal natural products and derivatives. Biological testing is also performed to evaluate their activity with the goal of creating new front-line agrochemicals. This pursuit allows graduate students to acquire specialized training in chemical synthesis and biological assays. This project additionally incorporates educational training for graduate student scientists interested in a diverse set of careers. Students are provided opportunities to participate in an innovative teaching program to diversify the workforce. Involvement in an educational program on consulting that leverages the existing entrepreneurial infrastructure at the university is also provided. The goal of this research project is to characterize and develop natural products and derivatives thereof for their implementation as inhibitors of agriculturally relevant pathogens. The target molecules are products found within the rhizosphere and have been exquisitely tuned to inhibit plant pathogens. Specifically, this project utilizes tools from synthetic organic chemistry, biochemistry, and microbiology to interrogate two specific natural products, promysalin and peniciaculin A. The compounds appear to act on plant pathogens as mimics of ubiquinone. Synthetic analogs are used to probe the molecular basis for the biological effects. By leveraging an understanding of the mechanistic targets of these natural products the research team is able to design and construct lead compounds for commercialization in the agrochemical industry.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

有了这个奖项，化学部的生命过程化学项目资助了埃默里大学的威廉·韦斯特博士，研究抗真菌的天然产物对枯萎病的活性。广义的定义是植物的疾病或伤害，其特征是部分形成病变、枯萎或死亡。其影响范围很广，从一种特定作物的广泛短缺到造成严重经济负担和社会困难的彻底饥荒。为了限制这些潜在的威胁，本研究中提出的工作使用化学来制造抗真菌的天然产物和衍生物。还进行了生物测试，以评估它们的活性，目标是创造新的一线农用化学品。这种追求使研究生能够获得化学合成和生物分析方面的专门训练。该项目还包括对对各种职业感兴趣的研究生科学家的教育培训。学生有机会参与创新的教学计划，以使劳动力多样化。还提供了参与咨询教育项目的机会，该项目利用了大学现有的创业基础设施。本研究项目的目标是表征和开发天然产物及其衍生物，以作为农业相关病原体的抑制剂。目标分子是在根际内发现的产物，并且已经被精细地调整以抑制植物病原体。具体来说，该项目利用合成有机化学、生物化学和微生物学的工具来研究两种特定的天然产物，丙沙林和青霉素a。这两种化合物似乎作为泛醌的模拟物作用于植物病原体。利用合成类似物探索生物效应的分子基础。通过利用对这些天然产物的机制目标的理解，研究团队能够设计和构建用于农化工业商业化的先导化合物。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。