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

非天然氨基酸已成功地掺入肽中，导致蛋白水解稳定性增加以及构象稳定性增加。 该项目的主要研究者开发了一种新的策略，用于从酶促水解前手性中间体得到的常见合成中间体制备各种各样的非天然氨基酸。这种策略允许使用简单的合成策略制备一系列非天然氨基酸。本研究将追求以下目标：a）从共同的中间体平行制备各种同手性相似的氨基酸，B）将选择的非天然氨基酸掺入到具有生物学意义的短肽中，以及c）研究掺入选择的非天然残基的肽的稳定性。本研究的一个关键目的是开发简单的策略，允许快速评估非天然氨基酸残基对肽稳定性的影响。这项研究计划将允许收集数据，这些数据可用于未来开发具有更高稳定性的肽。这些肽化合物可能在传感器和当前重要的其他材料中找到重要用途。本研究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数量的合成操作制备各种非天然氨基酸。这种方法不仅在生物有机化学和生物化学领域有用。该项目是一个跨学科的项目，将酶学、传统有机合成和生物化学领域合并为一个与生物科学相关的单一项目。更广泛的影响：该项目涉及培训、教育和推广活动。从这项研究中获得的信息将被纳入一个“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一些大学的本科课程。从该项目中获得的数据将被纳入“客座讲师”方案，并将用作向更广泛的受众传播信息的一种方法。该项目将允许研究生和本科生拓宽他们的研究经验，这将使他们在毕业后的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大的少数民族学生人口提供服务。

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.