Understanding Phosphoryl Transfer through Physical Organic Chemistry

通过物理有机化学了解磷酰基转移

• 批准号: EP/E01917X/1
• 负责人: Nicholas Williams
• 金额: $ 22.96万
• 依托单位: University of Sheffield
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FE01917X%2F1
• 关键词: Understanding; Phosphoryl; Transfer; through; Physical

The transfer of phosphate groups is at the heart of many biological processes. However, unless it is catalysed, they are among the slowest known biochemical reactions. To understand how biological catalysts manage to acclerate these reactions so efficiently requires an insight into the transition state structure - this is the species that must be stabilised to allow the reaction to proceed rapidly. We have defined some of the background characteristics of closely relevant phosphate esters, and need to extend these studies to reveal more detail. Then, using model systems, we shall investigate how specific interactions speed up the reaction and how they affect the probes we use to characterise the transition state. These studies will inform the interpretation of structural and kinetic data of biological catalysts, and help direct the design of more effective artificial catalysts that can be used within a biological context. Such catalysts have valuable potential as robust tools for use in molecular biology, particularly in manipulating DNA if they can be made efficient enough. The same approach and modifications shall be made with Zn based complexes that are already effective for cleaving RNA model compounds; the models will aid their development, and the analysis will establish where to focus further improvements.

磷酸基团的转移是许多生物过程的核心。然而，除非它被催化，否则它们是已知最慢的生化反应之一。要了解生物催化剂如何如此有效地加速这些反应，需要深入了解过渡态结构-这是必须稳定以使反应快速进行的物种。我们已经定义了一些密切相关的磷酸酯的背景特征，需要扩展这些研究以揭示更多细节。然后，使用模型系统，我们将研究特定的相互作用如何加速反应，以及它们如何影响我们用来表征过渡态的探针。这些研究将为生物催化剂的结构和动力学数据的解释提供信息，并帮助指导可在生物学背景下使用的更有效的人工催化剂的设计。这种催化剂作为分子生物学中使用的强大工具具有宝贵的潜力，特别是如果它们能够足够有效地操纵DNA。同样的方法和修改应与锌基复合物，已经有效地切割RNA模型化合物;模型将有助于他们的发展，分析将建立在哪里集中进一步改进。

项目成果

Catalytic zinc complexes for phosphate diester hydrolysis.

• DOI: 10.1002/anie.201400335
• 发表时间: 2014-07-28
• 期刊: ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
• 影响因子: 16.6
• 作者: Tirel, Emmanuel Y.;Bellamy, Zoe;Adams, Harry;Lebrun, Vincent;Duarte, Fernanda;Williams, Nicholas H.
• 通讯作者: Williams, Nicholas H.

Activating water: important effects of non-leaving groups on the hydrolysis of phosphate triesters.

活化水：非离去基团对磷酸三酯水解的重要影响。

• DOI: 10.1002/chem.201101926
• 发表时间: 2011
• 期刊: Chemistry (Weinheim an der Bergstrasse, Germany)
• 作者: Kirby AJ