Mechanistic Studies of Molecular Recognition of Methylated Lysine and Arginine

甲基化赖氨酸和精氨酸的分子识别机制研究

• 批准号: 1306977
• 负责人: Marcey Waters
• 金额: $ 42万
• 依托单位: University of North Carolina at Chapel Hill
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-10-01 至 2017-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1306977&HistoricalAwards=false
• 关键词: Mechanistic; Studies; Molecular; Recognition; Methylated

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Marcey Waters from the University of North Carolina at Chapel Hill to study the fundamental molecular recognition properties of a set of synthetic receptors for each of the methylation states of lysine (Lys) and arginine (Arg), which are protein modifications involved in the control of gene expression. The receptors will be developed using Dynamic Combinatorial Chemistry, which will allow for rapid identification of a set of differentially selective hosts. Comprehensive mechanistic studies will be performed in which both the host and guest are varied that will provide insight into mechanisms for selective recognition between closely related guests in aqueous solution. Lastly, these same receptors will be used in indicator displacement assays coupled with pattern recognition to characterize the enzymes that methylate Lys, providing new insight into these biological pathways.Molecular recognition, which involves the interaction of two (bio)molecules through a set of weak intermolecular forces called non-covalent interactions, is critical to virtually all biological function, including the interactions of proteins with other proteins, biomolecules, and inhibitors. However, the ability to predict the set of non-covalent interactions that will give rise to a particular molecular recognition event with a certain binding affinity and selectivity is still not possible. This work will provide a systematic study of a set of biologically relevant molecular recognition events to gain mechanistic insight into the features that provide both affinity and selectivity. This research will educate both graduate students and undergraduate students in organic, analytical, supramolecular chemistry, and biochemistry, providing a strong interdisciplinary background, which is necessary in an increasingly interdisciplinary workforce. This work will also introduce underrepresented high school and college students to interdisciplinary research.

有了这个奖项，化学部门的生命过程化学项目资助了北卡罗来纳大学教堂山分校的Marcey Waters博士，以研究一组合成受体对赖氨酸（Lys）和精氨酸（Arg）的每种甲基化状态的基本分子识别特性，这些受体是参与基因表达控制的蛋白质修饰。受体将使用动态组合化学开发，这将允许快速识别一组不同选择的宿主。将进行全面的机制研究，其中宿主和客体都是不同的，这将为水溶液中密切相关的客体之间的选择性识别机制提供见解。最后，这些相同的受体将用于指示剂置换试验，结合模式识别来表征甲基化赖氨酸的酶，为这些生物途径提供新的见解。分子识别涉及两个（生物）分子通过一组称为非共价相互作用的弱分子间力的相互作用，对几乎所有生物功能都至关重要，包括蛋白质与其他蛋白质、生物分子和抑制剂的相互作用。然而，预测一组非共价相互作用将产生具有一定结合亲和力和选择性的特定分子识别事件的能力仍然是不可能的。这项工作将提供一组生物学相关分子识别事件的系统研究，以获得对提供亲和力和选择性的特征的机制见解。这项研究将教育研究生和本科生有机、分析、超分子化学和生物化学，提供强大的跨学科背景，这是越来越多的跨学科劳动力所必需的。这项工作也将介绍代表性不足的高中和大学生跨学科的研究。