神经肽的靶向分析

项目名称： 神经肽的靶向分析

项目编号： No.21475128

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 数理科学和化学

项目作者： 张晓哲

作者单位： 中国科学院大连化学物理研究所

项目金额： 79万元

中文摘要： 神经肽作为肽类递质或荷尔蒙，是疾病早期诊断的高特异性分子标志物。为显著提高发现神经肽标志物的能力,本项目致力于发展高选择性的靶向神经肽组学技术。将发展目标肽的识别工作,以提高神经肽的鉴定率。为此,拟通过编程计算，分析一级质谱信息中数十万肽的质量特性和质量差异，或辅以衍生化的方法，识别出长链肽、二硫键肽等；然后进行靶向的高分辨质谱分析，在优化的条件下，获取目标肽的高质量二级质谱，进行测序。为识别出血液中的微量神经肽标志物，将利用糖尿病小鼠作为模式动物，先比较分析神经肽在器官如胰腺、大脑和肠胃中的特异性变化，通过模式识别和关联性分析发现异变的器官神经肽；然后以这些肽为目标，对血液进行富集处理和靶向的定量分析，验证神经肽变化与疾病进展的联系，进而发现常规血液检测所不能发现的微量神经肽标志物。本项目的实施有望将神经肽组学研究推向新的高度，并大大提升从血液这种常见临床样本中发现神经肽标志物的能力。

中文关键词： 神经肽；鉴定率；靶向分析；识别；糖尿病

英文摘要： Neuropeptides, which are peptide neurotransmitters or hormones found in the brain as well as various peripheral organs, play a critical role in controlling physiological processes. They can be highly specific biomarkers for the early diagnostics of various diseases. However, it remains technically challenging for the discovery of neuropeptide biomarkers for many reasons. To address this issue, our proposed neuropeptidomics study aims to perform an in-depth and comprehensive characterization of neuropeptides, particularly by using targeted liquid chromatography (LC)-mass spectrometry (MS) analysis. We will develop bioinformatics methods to recognize long chain neuropeptides and disulfide bonded neuropeptides, which are extremely rarely sequenced in the current neuropeptidomics. We will then use diabetes mouse as model to find a strategy that is able to discover neuropeptide biomarkers that are of low abundance in the blood. We will sequence neuropeptides in the pancreases, liver, gastroinstenine and brain from the control, early diabetes and diabetes mice. The identified peptides will be submitted to selective reaction monitoring (SRM) LC-MS analysis for quantify the levels of neuropeptides in different organs acquired from the mikes of different groups. Differential analysis will be performed to find the neuropeptides that are significantly altered due to the diabetes disease. The levels of these neuropeptides will be further examined in the blood of mice to very if they can act as blood biomarker for diabetes. The discovery of altered peptides will allow us to optimize and validate our neuropeptidomics approaches. The findings will also pave the way for identifying the possible neuropeptide biomarkers for many other diseases.

英文关键词： neuropeptide;identification rate;targeted analysis;recognition;diabetes