Artificial Glycosidases

人工糖苷酶

• 批准号: 1800239
• 负责人: James Cowan
• 金额: $ 42万
• 依托单位: Ohio State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-15 至 2021-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1800239&HistoricalAwards=false
• 关键词: Artificial; Glycosidases

Carbohydrates are among nature's most abundant biomolecules, with roles ranging from structural biopolymers to a multitude of cellular processes. Biomass is a potential source of renewable energy and a source of value-added small molecule products, but requires molecular catalysts capable of efficiently degrading these materials in ways that are more energy efficient and environmentally friendly. Such catalysts (glycosidases) have broad application in the pharmaceutical and food technology industries, as well as in the production of valuable fuel products. Dr. Cowan's research program provides training in a diverse and multidisciplinary array of experimental tools and techniques in areas of chemical, biological, and physical sciences. While the questions being addressed are primarily curiosity-driven, the research has broader relevance to areas of bimolecular recognition and catalysis. The most significant impact of any research endeavor is the development of intellectual capital that in turn is reinvested in society and the scientific work force of the future. To that end, Dr. Cowan has developed internship and training opportunities with local biotech businesses, and personally mentors K-12 and undergraduate trainees. Dr. Cowan is actively engaged in outreach activities that build upon his research to promote engagement of students in science, technology, engineering and mathematics (STEM) disciplines. These activities, which include summer research internships in Dr. Cowan's laboratory, are directed at improving the education of promising high school seniors and women students and encouraging their interest in STEM careers, as well outreach to local elementary schools and Cub Scout dens and packs.With funding from the Chemical Catalysis Program of the Chemistry Division, Dr. Cowan, of The Ohio State University, is developing artificial glycosidases that promote recognition and selective cleavage of complex oligosaccharides and carbohydrates. This work develops metallopeptides as glycosidase catalysts, and seeks a fundamental understanding of the structural basis for peptide-saccharide recognition that will guide the design of selective sugar-targeting catalysts. By use of nuclear magnetic resonance spectroscopy as a tool to determine structure, and isothermal titration calorimetry and surface plasmon resonance to evaluate binding energetics, Dr. Cowan and his coworkers are elucidating the role of specific amino acids in promoting sugar recognition and binding. Liquid chromatography and a variety of mass spectrometric methods are used to characterize catalyst reactivity, reaction products, and mechanism of action. Dr. Cowan's research program is developing catalysts for selective cleavage of oligo and polysaccharides, both as chemical tools for biochemical study, and for practical application in biomass degradation. His laboratory provides training in a diverse and multidisciplinary array of experimental tools and techniques in areas of chemical, biological, and physical science, including analytical reasoning. While the questions being addressed are primarily curiosity-driven, it is reasonable to expect that a fuller understanding of carbohydrate recognition and efficient catalytic degradation of stable sugar molecules has broader relevance to areas of bimolecular recognition and catalysis. The most significant impact of any research endeavor is the development of intellectual capital that in turn is reinvested in society and the scientific work force of the future. To that end, Dr. Cowan has developed internship and training opportunities with local biotech businesses, and personally mentors K-12 and undergraduate trainees. Dr. Cowan is actively engaged in outreach activities that build upon his research to promote engagement of students in science, technology, engineering and mathematics (STEM) disciplines. These activities, which include summer research internships in Dr. Cowan?s laboratory, are directed at improving the education of promising high school seniors and women students and encouraging their interest in STEM careers, as well outreach to local elementary schools and Cub Scout dens and packs.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

碳水化合物是自然界中含量最丰富的生物分子之一，其作用范围从结构生物聚合物到多种细胞过程。生物质是一种潜在的可再生能源和增值小分子产品的来源，但需要能够以更节能和更环保的方式有效地降解这些材料的分子催化剂。这类催化剂(糖苷酶)在制药和食品技术工业以及生产有价值的燃料产品中有广泛的应用。考恩博士的研究计划在化学、生物和物理科学领域提供各种不同和多学科的实验工具和技术培训。虽然所讨论的问题主要是好奇心驱动的，但这项研究与双分子识别和催化领域具有更广泛的相关性。任何研究努力最重要的影响是智力资本的发展，而智力资本反过来又被重新投资于社会和未来的科学工作力量。为此，考恩博士开发了当地生物技术企业的实习和培训机会，并亲自指导K-12和本科生。考恩博士积极参与以他的研究为基础的外展活动，以促进学生对科学、技术、工程和数学(STEM)学科的参与。这些活动包括考恩博士实验室的暑期研究实习，旨在改善有前途的高中生和女学生的教育，鼓励他们对STEM职业的兴趣，以及与当地小学和幼崽童子军窝点和群体的联系。在化学部化学催化项目的资助下，俄亥俄州立大学的考恩博士正在开发人造糖苷酶，以促进对复杂低聚糖和碳水化合物的识别和选择性切割。这项工作开发了金属多肽作为糖苷酶催化剂，并寻求对多肽-糖识别的结构基础的基本了解，这将指导选择性糖靶向催化剂的设计。通过使用核磁共振光谱作为确定结构的工具，并使用等温滴定量热法和表面等离子体共振来评估结合能，Cowan博士和他的同事们正在阐明特定氨基酸在促进糖识别和结合方面的作用。用高效液相色谱和多种质谱学方法表征了催化剂的反应性、反应产物和作用机理。考恩博士的研究计划正在开发选择性裂解寡糖和多糖的催化剂，既可以作为生化研究的化学工具，也可以用于生物质降解的实际应用。他的实验室在化学、生物和物理科学领域提供多样化和多学科的实验工具和技术培训，包括分析推理。虽然所讨论的问题主要是好奇心驱动的，但有理由预计，对碳水化合物识别和稳定糖分子的有效催化降解的更充分理解与双分子识别和催化领域具有更广泛的相关性。任何研究努力最重要的影响是智力资本的发展，而智力资本反过来又被重新投资于社会和未来的科学工作力量。为此，考恩博士开发了当地生物技术企业的实习和培训机会，并亲自指导K-12和本科生。考恩博士积极参与以他的研究为基础的外展活动，以促进学生对科学、技术、工程和数学(STEM)学科的参与。这些活动包括考恩？S博士实验室的暑期研究实习，旨在改善有前途的高中生和女学生的教育，鼓励他们对STEM职业的兴趣，以及与当地小学和童子军窝点和群体的接触。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。