CAREER: Bioorganic Research at USM. Development of Novel Somatostatin and Neurotensin Analogues

职业:USM 生物有机研究。

基本信息

  • 批准号:
    0844478
  • 负责人:
  • 金额:
    $ 82.5万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
    Standard Grant
  • 财政年份:
    2009
  • 资助国家:
    美国
  • 起止时间:
    2009-07-01 至 2016-01-31
  • 项目状态:
    已结题

项目摘要

Amino acids are the building blocks of life and are used in biology to prepare important materials of various types (i.e. proteins, peptides, hormones, etc). Small peptides have shown to be biologically active and can be used in a variety of situations. However, small peptides are frequently degraded by the presence of endogenous enzymes ultimately reducing their ability to achieve their biological function in an efficient manner. Unnatural amino acids, i.e. amino acids that are either not found or only rarely found in nature, have shown an ability to impart stability to small peptides towards enzymatic degradation. The Masterson Research Group (MRG) is particularly interested in two small peptides (Somatostatin and Neurotensin), which show a wide range of biological activity. The MRG has developed techniques that allow for the preparation of a variety of unnatural amino acids from a common synthetic intermediate. The synthetic strategy developed by the MRG allows for the parallel preparation of a variety of unnatural amino acids of importance to Somatostatin and Neurotensin. The unnatural amino acids will be used to replace specific amino acids in Somatostatin and Neurotensin. The peptide analogues will be tested for their ability to resist degradation by enzymes and for their ability to carry out their biological function. It is a key aim of this research to expand the scope of the techniques developed by the MRG to prepare a wide variety of novel unnatural amino acids and study their effect on peptide stability and function.Broader Impacts of the Project: The methods developed in this research will have a broad impact to the scientific community by providing efficient methods of preparing unnatural amino acids. The peptides prepared in this project will also provide valuable information on the structure-function relationships for Somatostatin and Neurotensin. The methods and materials will find broad applicability in bioorganic and materials sciences. The project is an interdisciplinary project that merges the areas of enzymology, traditional organic synthesis, biological chemistry, and mass spectrometry into a single project relevant to the biological sciences and chemistry. The project will allow for the training of the next generation of scientists in the state of Mississippi and will provide significant educational opportunities for graduate research assistants, undergraduate students, and economically disadvantaged high school student participants. The project will use some of the developed methodology from the MRG to teach a class at the graduate level. The class is titled "Mass Spectrometry: Useful for more than m/z" and will train graduate students on the use of NSF-funded mass spectrometry facilities at USM. The course will utilize an assay developed in the MRG to determine enantioselectivity from an enzymatic hydrolysis reaction (a process that is central to the synthetic methodology described above). The students will learn how to use the facilities so that they can make use of them in their own research endeavors and the MRG will be able to use the course to obtain the much needed data from the assays that the students will perform during the course. Mass spectrometry has become a routine method of analyzing a variety of molecules and the students who successfully complete the course will have gained skills that are transferable to a variety of job opportunities. The acquired skills will make the students highly competitive in an ever changing global job market.
氨基酸是生命的基石,在生物学中用于制备各种类型的重要物质(即蛋白质、肽、激素等)。小肽已被证明具有生物活性,可用于各种情况。然而,小肽经常被内源性酶降解,最终降低了它们以有效方式实现其生物功能的能力。非天然氨基酸,即在自然界中没有发现或很少发现的氨基酸,已经显示出赋予小肽酶降解稳定性的能力。Masterson研究小组(MRG)对两种小肽(生长抑素和神经紧张素)特别感兴趣,它们显示出广泛的生物活性。MRG已经开发了一种技术,允许从一种常见的合成中间体制备各种非天然氨基酸。MRG开发的合成策略允许平行制备各种对生长抑素和神经紧张素重要的非天然氨基酸。这些非天然氨基酸将用于替代生长抑素和神经紧张素中的特定氨基酸。将测试肽类似物抵抗酶降解的能力和执行其生物功能的能力。本研究的主要目的是扩大MRG开发的技术范围,以制备各种新型非天然氨基酸,并研究它们对肽稳定性和功能的影响。该项目的更广泛影响:本研究中开发的方法将通过提供制备非天然氨基酸的有效方法,对科学界产生广泛影响。该项目制备的肽也将为研究生长抑素和神经紧张素的结构-功能关系提供有价值的信息。这些方法和材料将在生物有机科学和材料科学中找到广泛的适用性。该项目是一个跨学科项目,将酶学、传统有机合成、生物化学和质谱学领域融合到一个与生物科学和化学相关的单一项目中。该项目将为密西西比州的下一代科学家提供培训,并将为研究生研究助理、本科生和经济状况不佳的高中生参与者提供重要的教育机会。该项目将使用MRG开发的一些方法来教授研究生水平的课程。这门课的题目是“质谱:对超过m/z有用”,将培训研究生在USM使用美国国家科学基金会资助的质谱设备。本课程将利用MRG中开发的一种测定方法来确定酶水解反应的对映体选择性(这一过程是上述合成方法的核心)。学生将学习如何使用这些设备,以便他们能够在自己的研究工作中使用这些设备,而MRG将能够使用本课程从学生在课程中进行的分析中获得所需的数据。质谱法已成为分析各种分子的常规方法,成功完成课程的学生将获得可用于各种工作机会的技能。获得的技能将使学生在不断变化的全球就业市场上具有很强的竞争力。

项目成果

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Douglas Masterson其他文献

Douglas Masterson的其他文献

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{{ truncateString('Douglas Masterson', 18)}}的其他基金

Equipment: MRI: Track 1 Acquisition of an Orbitrap Exploris 240 High-Resolution LC-MS for Research, Education, and Outreach at The University of Southern Mississippi (USM)
设备: MRI:轨道 1 采购 Orbitrap Exploris 240 高分辨率 LC-MS,用于南密西西比大学 (USM) 的研究、教育和推广
  • 批准号:
    2319932
  • 财政年份:
    2023
  • 资助金额:
    $ 82.5万
  • 项目类别:
    Standard Grant
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
  • 财政年份:
    2007
  • 资助金额:
    $ 82.5万
  • 项目类别:
    Standard Grant

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