Characterizing Neuropeptides with Chiral Modifications

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，被认为是生物激活肽。被研究的生物系统是加利福尼亚海杉的单个神经元。有三种建议的方法：仪器，酶和免疫。在第一，手性分离方法将被用来试图解决非对映异构体肽的D/L异构化的氨基酸之一。其次，利用仅能切割l -氨基酸的n端肽酶，利用基质辅助激光解吸电离质谱（MALDI）对片段进行分析。第三种方法是尝试培养针对含有d -氨基酸的肽的抗体。目标是发现新的含有d -氨基酸的肽在神经学上起作用。这个实验室的学生接受分析化学和神经生物学的训练。大脑和神经系统中的信号在很大程度上是由大量的肽完成的，其中许多尚未被发现。被充分研究的海芋蜗牛系统给研究人员提供了一个已经知道很多的模型系统。这个项目的成功将使我们更好地理解神经化学中的多肽，以及阿尔茨海默氏症等神经疾病，也将有助于在生物学和药学的其他问题的分析方法的进步。

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.