Mechanistic Studies of New C-S Bond Formation Chemistries

新型 C-S 键形成化学的机理研究

• 批准号: 1309148
• 负责人: Pinghua Liu
• 金额: $ 38万
• 依托单位: Trustees of Boston University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1309148&HistoricalAwards=false
• 关键词: Mechanistic; Studies; New; Bond; Formation

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Pinghua Liu from Boston University to study the mechanism of the oxidative C-S bond formations in ergothioneine and ovothiol biosyntheses. Thiol-containing molecules play many important roles in biological systems. The oxidative C-S bond formations in ergothioneine and ovothiol biosyntheses (EgtB-catalysis and OvoA catalysis) were first reported in late 2010 and early 2011 by Seebeck and co-workers. In preliminary studies on OvoA-catalysis, the Liu Group discovered three more new chemistries of these enzymes. With support from this award, they will carry out detailed mechanistic studies by integrating tools from various disciplines, including organic synthesis, molecular biology, bioinformatics, and enzymology. The goals are to differentiate among selected oxidative C-S bond formation mechanistic options. Then, through a combination of synthetic chemistry, pre-steady state kinetics, and spectroscopy techniques, they will trap and characterize some of the proposed intermediates. Information from this study will provide insights into the mechanism of the reactions of this new type of C-S bond formation.Representing about 1% of cell dry weight, sulfur adds considerable functionality to a wide variety of biomolecules. The thiol-imidazole functionality in ergothioneine and ovothiol makes them unique relative to other naturally occurring thiols. As a result, ergothioneine is proposed to play many beneficial roles in cellular functions. Information gained in this study will not only provide mechanistic insights on C-S bond formation chemistries (one of the frontiers in enzymology), but also help studies in related areas (e.g., investigating the physiological roles of these important metabolites). The interdisciplinary nature of the proposed work (organic synthesis, molecular biology, bioinformatics and enzymology) will provide an ideal opportunity to train high school students, undergraduates, and graduate students for research at the interface of Chemistry and Biology.

通过该奖项，化学司的化学过程计划正在为波士顿大学的Pinghua Liu博士提供资金，以研究埃尔戈氨酸和卵菌生物合成中氧化C-S键形成的机制。含硫醇的分子在生物系统中起许多重要的作用。 Ergothion和Ovothiol Biosyntheses中的氧化C-S键形成（EGTB催化和卵子催化）于2010年底首次由Seebeck及其同事报道。在有关OVOA催化的初步研究中，刘集团发现了这些酶的三种新化学。在该奖项的支持下，他们将通过整合来自各种学科的工具，包括有机合成，分子生物学，生物信息学和酶学，进行详细的机械研究。目标是区分选定的氧化C-S键形成机械选项。然后，通过合成化学，稳态态动力学和光谱技术的结合，它们将捕获并表征一些提出的中间体。这项研究的信息将提供有关这种新型C-S键形成反应机制的见解。硫磺约占细胞干重约1％，为各种生物分子增添了相当大的功能。甲醇 - 咪唑在甲氨酸和卵硫醇中的功能使其相对于其他天然硫醇而独特。 结果，提议ergotheine在细胞功能中起许多有益的作用。在这项研究中获得的信息不仅将提供有关C-S键形成化学（酶学的前沿）的机械见解，还可以帮助研究相关领域的研究（例如，研究这些重要代谢物的生理作用）。拟议工作的跨学科性质（有机合成，分子生物学，生物信息学和酶学）将为培训高中生，本科生和研究生提供理想的机会，以在化学和生物学界面进行研究。