INTERNATIONAL COLLABORATION IN CHEMISTRY: THE DEVELOPMENT OF CHEMICAL PROBES FOR HOPANOID FUNCTION

化学领域的国际合作：开发霍帕尼功能化学探针

• 批准号: EP/K000888/1
• 负责人: Stuart Conway
• 金额: $ 37.48万
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2013
• 资助国家: 英国
• 起止时间: 2013 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FK000888%2F1
• 关键词: INTERNATIONAL; COLLABORATION; CHEMISTRY; DEVELOPMENT; CHEMICAL

We are interested in studying a set of chemicals found in bacteria called hopanoids. These chemicals were thought to be 'molecular fossils' that provided information on the evolution of how bacteria processed chemicals and obtained energy. However, recent work has shown that the function of hopanoids is more complex than originally thought. Indeed, it seems likely that hopanoids still play an important role in recent bacteria. In order to understand better the function of hopanoids we are planning to make new and unnatural hopanoid derivatives that have additional functions that will assist these studies. We plan to make fluorescent ('glow in the dark') hopanoids that will allow us to study where they are found in cells. We also plan to make molecular 'fishing rods', using hopanoids as the 'bait', to determine what other molecules, especially proteins, that hopanoids interact with in cells. These chemical 'probes' will allow us to understand how the hopanoids exert their effects within cells and may potentially identify new targets for harming bacteria, which will be interesting for the development of antibiotics.

我们感兴趣的是研究在细菌中发现的一组化学物质，称为Hopanoid。这些化学物质被认为是“分子化石”，为细菌处理化学物质和获取能量的进化提供了信息。然而，最近的研究表明，Hopanoid的功能比最初想象的要复杂得多。事实上，类霍普诺素似乎仍然在最近的细菌中扮演着重要的角色。为了更好地了解何首乌的功能，我们正计划制造新的和非天然的何首乌衍生物，它们具有额外的功能，将有助于这些研究。我们计划制造荧光的(在黑暗中发光的)霍普诺德，这将使我们能够研究它们在细胞中的位置。我们还计划制造分子“钓鱼杆”，以荷叶菊素为“诱饵”，以确定荷叶菊素在细胞中与哪些其他分子，特别是蛋白质相互作用。这些化学“探针”将使我们能够了解霍帕诺类化合物是如何在细胞内发挥作用的，并可能确定伤害细菌的新靶点，这对抗生素的开发将是有趣的。

项目成果

Pyocyanin degradation by a tautomerizing demethylase inhibits Pseudomonas aeruginosa biofilms.

• DOI: 10.1126/science.aag3180
• 发表时间: 2017-01-13
• 期刊: Science (New York, N.Y.)
• 作者: Costa KC;Glasser NR;Conway SJ;Newman DK
• 通讯作者: Newman DK

Quantitative hopanoid analysis enables robust pattern detection and comparison between laboratories.

• DOI: 10.1111/gbi.12132
• 发表时间: 2015-07
• 期刊: Geobiology
• 影响因子: 3.7
• 作者: Wu CH;Kong L;Bialecka-Fornal M;Park S;Thompson AL;Kulkarni G;Conway SJ;Newman DK
• 通讯作者: Newman DK