Mimetic sugar nucleotides to probe a strategic bacterial dehydrogenase enzyme

模拟糖核苷酸探测战略细菌脱氢酶

• 批准号: EP/P000762/1
• 负责人: Gavin Miller
• 金额: $ 31.34万
• 依托单位: Keele University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FP000762%2F1
• 关键词: Mimetic; sugar; nucleotides; probe; strategic

This work will use exploratory scientific research to help further understand the way that the infectious bacterium and opportunistic pathogen, P. aeruginosa, regulates its own biosynthetic processes. Infections caused by P. aeruginosa are particularly harmful for sufferers of cystic fibrosis and one critical process that this bacterium utilises here is the production of a protective biofilm, which contributes to the ineffectiveness of standard antibiotic treatments used against it. Bacterial biofilm formation processes are governed by enzymes, which control the formation of key biological building blocks for assembly into the more complex, ultimate biofilm system. It is here that organic chemists can use their expertise to build new molecules to mimic the building blocks used by bacteria, effectively creating a molecular tool to investigate and understand a given enzyme mechanism in more detail. The molecular tools needed to do this are called sugar nucleotides and their construction is an intricate, exciting and diverse activity. Using such tools, important new information about enzyme structure and function can be collected, which could contribute towards instigating new approaches to disrupt specific enzyme activity and potentially arrest normal bacterial biofilm development. It is the purpose of this research to initiate an essential, molecular-level understanding of how a critical enzyme-controlled process operates within this pathogen.

这项工作将使用探索性科学研究来帮助进一步了解感染性细菌和机会致病菌铜绿假单胞菌调节其自身生物合成过程的方式。由铜绿假单胞菌引起的感染对囊性纤维化患者特别有害，这种细菌在这里利用的一个关键过程是产生保护性生物膜，这导致针对它的标准抗生素治疗无效。细菌生物膜形成过程由酶控制，酶控制关键生物构件的形成，以组装成更复杂的，最终的生物膜系统。正是在这里，有机化学家可以利用他们的专业知识来构建新的分子来模拟细菌使用的构建模块，有效地创造一种分子工具来更详细地研究和理解给定的酶机制。完成这一过程所需的分子工具被称为糖核苷酸，它们的构建是一项复杂、令人兴奋和多样化的活动。使用这些工具，可以收集有关酶结构和功能的重要新信息，这可能有助于激发新的方法来破坏特定的酶活性并可能阻止正常的细菌生物膜发育。这项研究的目的是启动一个重要的，分子水平的了解如何在这种病原体的关键酶控制的过程中运作。

项目成果

Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase.

• DOI: 10.3762/bjoc.18.142
• 发表时间: 2022
• 期刊: Beilstein journal of organic chemistry
• 影响因子: 2.7
• 作者: Ahmadipour S;Wahart AJC;Dolan JP;Beswick L;Hawes CS;Field RA;Miller GJ
• 通讯作者: Miller GJ

Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase

C6 修饰的甘露糖 1-磷酸酯的合成以及衍生糖核苷酸针对 GDP-甘露糖脱氢酶的评估

• DOI: 10.3762/bxiv.2022.57.v1
• 发表时间: 2022
• 作者: Ahmadipour S

6R/S-deutero-a-d-mannopyranoside 1-phosphate

6R/S-氘代-a-d-吡喃甘露糖苷1-磷酸

• DOI: 10.3390/m1068
• 发表时间: 2019
• 期刊: Molbank
• 影响因子: 0.6
• 作者: Ahmadipour S