Characterizing Neuropeptides with Chiral Modifications

表征具有手性修饰的神经肽

• 批准号: 0400768
• 负责人: Jonathan Sweedler
• 金额: $ 59万
• 依托单位: University of Illinois at Urbana-Champaign
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-08-15 至 2009-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0400768&HistoricalAwards=false
• 关键词: Characterizing; Neuropeptides; Chiral; Modifications

Professor Jonathan Sweedler of the U of Ill Urbana-Champaign is supported by the Analytical and Surface Chemistry Program to analyze a chiral post-translational modification in neuropeptides, namely, an L to D isomerization thought to activate the peptide biologically. The biological system under study is the single neuron of Aplysia californica. There are three proposed approaches: instrumental, enzymatic and immunological. In the first, chiral separation methods will be used to try to resolve diastereomeric peptides that differ by D/L isomerization of one of the amino acids. Secondly, N-terminal peptidases that cleave only L-amino acids will be used followed by analysis of fragments by matrix-assisted laser desorption ionization mass spectrometry (MALDI). A third approach is to attempt to grow antibodies to peptides containing D-amino acids. The goal is to discover new D-amino acid containing peptides that function neurologically. Students in this laboratory are trained in analytical chemistry and neurobiology. Signaling in the brain and nervous system is accomplished to a large extent by a vast number of peptides, many as yet undiscovered. The well studied Aplysia snail system gives researchers one model system that a great deal is already known about. Success of this project will allow a better understanding of peptides in neurochemistry, as well as in neurological diseases such as Alzheimer's, and will also contribute to advances in analytical methods for other questions in biology and pharmacy.

伊利诺伊大学厄巴纳-香槟分校的 Jonathan Sweedler 教授在分析和表面化学项目的支持下分析了神经肽的手性翻译后修饰，即 L 到 D 异构化，被认为可以从生物学角度激活肽。 所研究的生物系统是加州海兔的单个神经元。 提出了三种方法：仪器方法、酶方法和免疫方法。 首先，将使用手性分离方法来尝试解析因其中一个氨基酸的 D/L 异构化而不同的非对映异构肽。 其次，将使用仅裂解 L-氨基酸的 N 端肽酶，然后通过基质辅助激光解吸电离质谱 (MALDI) 分析片段。 第三种方法是尝试培养针对含有 D-氨基酸的肽的抗体。 目标是发现具有神经功能的新的含有 D-氨基酸的肽。 该实验室的学生接受分析化学和神经生物学方面的培训。 大脑和神经系统中的信号传导在很大程度上是由大量肽完成的，其中许多肽尚未被发现。 经过深入研究的海兔系统为研究人员提供了一种已知的模型系统。 该项目的成功将使人们更好地了解神经化学以及阿尔茨海默氏症等神经系统疾病中的肽，并且还将有助于生物学和药学其他问题的分析方法的进步。