Novel Preparation of Various Unnatural Amino Acids and Their Incorporation Into Peptides of Biological Significance

各种非天然氨基酸的新制备及其与具有生物意义的肽的结合

• 批准号: 0639817
• 负责人: Douglas Masterson
• 金额: --
• 依托单位: University of Southern Mississippi
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0639817&HistoricalAwards=false
• 关键词: Novel; Preparation; Various; Unnatural; Amino

Unnatural amino acids have been successfully incorporated into peptides resulting in increased proteolytic stability as well as increased conformational stability. The principal investigator of this project has developed a novel strategy for the preparation of a wide variety of unnatural amino acids from a common synthetic intermediate derived from an enzymatic hydrolysis of a prochiral intermediate. This strategy allows for the ready preparation of a series of unnatural amino acids using straightforward synthetic strategies. This research will pursue the following goals: a) the parallel preparation of various homochirally similar amino acids from a common intermediate, b) the incorporation of select unnatural amino acids into short peptides of biological significance, and c) study the stability of the peptides incorporating select unnatural residues. It is a key aim of this research to develop straightforward strategies that allow for the rapid evaluation of the effect of unnatural amino acid residues on peptide stability. This research program will allow for the gathering of data which can be used in the future to develop peptides with increased stability. These peptide compounds may find significant use in sensors, and other materials of current importance. The synthetic methods developed in this research will have a broad impact to the scientific community in that it will allow for the preparation of a wide range of unnatural amino acids using a minimal number of synthetic manipulations. This methodology will find use not only in the area of bioorganic and biological chemistry. This project is an interdisciplinary project that merges the areas of enzymology, traditional organic synthesis, and biological chemistry into a single project relevant to the biological sciences.Broader Impacts: The project involves training, educational and outreach activities. The information derived from this research will be incorporated into a "guest lecturer" program that will incorporate the topic of enzymes as catalysts for organic synthesis in the undergraduate curriculum at a number of universities. The data obtained from this project will be incorporated into the "guest lecturer" program and will be used as a method of disseminating the information to a more general audience. This project will allow for graduate and undergraduate students to broaden their research experiences which will make them competitive in the biotechnology job market following graduation. This project will have an impact on underrepresented minority groups within the state of Mississippi as The University of Southern Mississippi serves a relatively large minority student population.

非天然氨基酸已成功掺入肽中，从而增加了蛋白水解稳定性以及构象稳定性。 该项目的主要研究人员开发了一种新策略，用于从前手性中间体的酶水解衍生的常见合成中间体制备多种非天然氨基酸。该策略允许使用简单的合成策略来准备一系列非天然氨基酸。本研究将追求以下目标：a）从共同的中间体中平行制备各种同手性相似的氨基酸，b）将选定的非天然氨基酸掺入具有生物学意义的短肽中，以及c）研究掺入的肽的稳定性选择非天然残基。这项研究的一个主要目标是开发简单的策略，以便快速评估非天然氨基酸残基对肽稳定性的影响。该研究计划将收集数据，这些数据可在未来用于开发稳定性更高的肽。这些肽化合物可能在传感器和其他当前重要的材料中发挥重要作用。这项研究中开发的合成方法将对科学界产生广泛的影响，因为它将允许使用最少的合成操作来制备各种非天然氨基酸。该方法不仅可用于生物有机和生物化学领域。该项目是一个跨学科项目，它将酶学、传统有机合成和生物化学领域合并为与生物科学相关的单个项目。更广泛的影响：该项目涉及培训、教育和外展活动。从这项研究中获得的信息将被纳入“客座讲师”计划，该计划将把酶作为有机合成催化剂的主题纳入许多大学的本科课程中。从该项目获得的数据将被纳入“客座讲师”计划，并将用作向更广泛的受众传播信息的方法。该项目将使研究生和本科生能够扩大他们的研究经验，这将使他们在毕业后在生物技术就业市场上具有竞争力。该项目将对密西西比州内代表性不足的少数群体产生影响，因为南密西西比大学为相对较多的少数族裔学生群体提供服务。