CAREER: A Systematic Investigation of Protein-Septanose Interactions

职业生涯：蛋白质-七糖相互作用的系统研究

• 批准号: 0546311
• 负责人: Mark Peczuh
• 金额: $ 55万
• 依托单位: University of Connecticut
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-01 至 2012-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0546311&HistoricalAwards=false
• 关键词: CAREER; Systematic; Investigation; Protein; Septanose

With the support of the Organic and Macromolecular Chemistry Program, Professor Mark Peczuh, of the Department of Chemistry at the University of Connecticut, will study the interactions between lectins and unnatural seven membered ring sugars (septanoses). Integral to the approach will be the development of structure activity relationships among a number of septanose-containing carbohydrates based on their relative affinities to the target proteins. A combination of organic synthesis, conformational analysis, and binding studies will be used to determine how septanoses are recognized. Interactions will be evaluated by conducting isothermal titration calorimetry (ITC) and NMR Saturation Transfer Difference (STD) experiments using the synthesized septanose sugars and Concanavalin A (ConA) and Maltose Binding Protein (MBP). The results of these investigations will elucidate how proteins recognize the unnatural sugars and provide a starting point for the development of septanose-based inhibitors of protein function.The Organic and Macromolecular Chemistry program is supporting Professor Mark Peczuh of the Department of Chemistry at the University of Connecticut who will concurrently investigate septanose conformational preferences and protein-septanose binding behavior that will rapidly provide key information for understanding protein-carbohydrate interactions generally and will motivate the design of septanose carbohydrates with potential therapeutic applications. The research will also train students in the theoretical and technical aspects of experimental bioorganic chemistry. Professor Peczuh will also work to dispel common misconceptions about science and scientists among the public by making science more accessible to a broader audience, which should increase interest in the sciences and lead to well reasoned corporate and public policy. Thus, a 'Chemistry in Literature' course taught in conjunction with the English Department will explore the dynamic and creative nature of the scientific process, the generality of analytical thinking, and the idea that discovery is a human process influenced by societal as well as scientific pressures. The course is designed to impact a diverse target audience to maximize its effectiveness.

在有机和大​​分子化学计划的支持下，康涅狄格大学化学系的Mark Peczuh教授将研究凝集素与不自然的七个成员环糖（Septanoses）之间的相互作用。 该方法不可或缺的是，基于其与靶蛋白的相对亲和力，许多含有隔膜的碳水化合物之间的结构活性关系的发展。 有机合成，构象分析和结合研究的结合将用于确定如何识别隔膜。 相互作用将通过进行等温滴定量热法（ITC）和NMR饱和转移差异（STD）实验，并使用合成的隔糖糖和contanavalin a（CONA）和麦芽糖结合蛋白（MBP）进行评估。这些研究的结果将阐明蛋白质如何识别非自然的糖，并为开发基于隔糖浆的蛋白质功能抑制剂的发展提供了一个起点。蛋白质 - 碳水化合物相互作用通常会激励使用潜在的治疗应用的隔糖碳水化合物的设计。该研究还将培训学生在实验生物有机化学的理论和技术方面进行培训。 Peczuh教授还将通过使更广泛的受众范围更容易获得科学，从而消除对科学和公众科学家的共同误解，这应该增加对科学的兴趣，并导致有理由的公司和公共政策。 因此，与英语系结合教授的“文学化学”课程将探讨科学过程的动态和创造性，分析思维的一般性以及发现是受社会和科学压力影响的人类过程的观念。 该课程旨在影响多样化的目标受众以最大程度地提高其有效性。