复杂蛋白聚糖序列分析

项目名称： 复杂蛋白聚糖序列分析

项目编号： No.81473179

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 张真庆

作者单位： 苏州大学

项目金额： 80万元

中文摘要： 蛋白聚糖是一类广泛参与生命和病理过程的复杂大分子，它由一个蛋白核和一条或多条糖胺聚糖链共价结合而成。对于已有的和潜在的蛋白聚糖或糖胺聚糖药物来说它复杂的序列和结构一直以来都限制着药物学家对它们的深入研究,Decorin就是最典型的蛋白聚糖代表之一。该课题将针对这类大分子建立有效的序列分析方法和策略。申请人将利用离子色谱、反相离子对液质联用建立有效、灵敏和稳定的复杂糖基组成分析方法，同时利用多种液质联用和不同二级质谱方法(CAD和ETD)建立对较大聚合度寡糖高效和灵敏的序列分析方法。在此基础上，申请人将通过不同方式获取不同来源的Decorin（它们有着不同的糖链组成和序列），并分别以它们为研究对象进行精确的序列分析。该工作将建立一系列复杂糖胺聚糖序列分析方法，进而描绘出几个不同来源Decorin糖链的序，最后促进复杂糖链的糖组学研究和蛋白聚糖/糖胺聚糖类药物的发展。

中文关键词： 蛋白聚糖；糖组学；液质联用；二级质谱；序列分析

英文摘要： Proteoglycans (PGs), composed of one protein core and one or several glycosaminoglycan (GAG) chains with covalent bond, participate in and regulate many physiological and pathophysiological processes. However, their complicated seqences and structures have been challenging the analysts for a long time, so that it is hard to clarify the mechanisms of existed and/or potential PG/GAG drugs. Decorin, a proteoglycan, is one of the most important cell regulators observed in tumor microenvironment. It is regarded as a potential cancer biomarker and antitumer reagent by many pharmacologists. This project will focus on the analytical methods and strategies to sequence these complex PGs/GAGs. In this project, different ion chromatography and ion-pair reverse-phase chromatography coulpled with high resolution mass spectrometry will be developed and applied to analyze the composition of these complex glycans. In addition, various LC methods/technologies coupled with different MS/MS technologies (CAT and ETD) will be develped to sequence the big GAG oligosaccharides. Based on the work, Decorins from different sources, which have different sugar compositon and sequences, will be sequenced. This work will develop a serious of analytical methods; figure out the detailed sequences of several Decorins; promote the glycomics for PGs/GAGs; and lead the PGs/GAGs drug development.

英文关键词： Proteoglycan;Glycomics;LC-MS;MS/MS;Sequencing Analysis