Design of Reaction Catalysts Based on Protein Cavities

基于蛋白质空腔的反应催化剂设计

• 批准号: 9807495
• 负责人: Mark Distefano
• 金额: $ 27.32万
• 依托单位: University of Minnesota-Twin Cities
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 2001-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9807495&HistoricalAwards=false
• 关键词: Design; Reaction; Catalysts; Based; Protein

With this Renewal award, the Organic and Macromolecular Chemistry Program is continuing support for Dr. Mark Distefano at the University of Minnesota - Twin Cities. The objectives of the work are to: 1) improve the activities and enantioselectivities of transaminating catalysts based on protein cavities of mutant FABPs (Fatty Acid Binding Proteins), 2) assess the effects of cofactor structure, 3) expand the scope of reaction types to include C-C bond formation, 4) develop methods to prepare and screen rapidly catalyst candidates, and 5) develop a phage display system to select protein cavities that can bind pyridoxamine analogues noncovalently. Dr. Distefano is developing a series of novel semisynthetic enzyme-like catalysts based on a class of proteins (FABPs) that contain a large empty central cavity, which can be used to hold organic substrates while they are operated on by cofactors that are chemically linked to the protein. The FABPs can be easily cloned and efficiently expressed, allowing considerable variability in their size and composition. Such catalysts could be very useful in the preparation of a wide variety of specialty chemicals. Because they operate in water under mild conditions and are prepared from biodegradable materials, they are also environmentally attractive.

凭借这一续展奖，有机和高分子化学项目将继续支持明尼苏达大学双城分校的 Mark Distefano 博士。 这项工作的目标是：1) 提高基于突变 FABP（脂肪酸结合蛋白）蛋白腔的转氨催化剂的活性和对映选择性，2) 评估辅因子结构的影响，3) 扩大反应类型范围，包括 C-C 键形成，4) 开发快速制备和筛选候选催化剂的方法，5) 开发噬菌体展示系统来选择可以结合的蛋白腔 非共价吡哆胺类似物。 Distefano 博士正在开发一系列基于一类蛋白质 (FABP) 的新型半合成类酶催化剂，这些蛋白质包含一个大的空中心空腔，可用于容纳有机底物，同时通过与蛋白质化学连接的辅助因子进行操作。 FABP 可以轻松克隆并有效表达，其大小和组成具有相当大的可变性。 这种催化剂对于制备多种特种化学品非常有用。 由于它们在温和条件下在水中运行并且由可生物降解材料制成，因此也具有环保吸引力。