中文摘要
蛋白质糖基化修饰的在生物体内具有非常重要作用,但一直缺乏一种高通量技术可在组学水平上观测生物体内糖链结构的变化,如果这一领域得到攻克,可以很大程度的帮助生物学家重新认识糖及其结构在生物体中的作用。国际上非常关注糖组学的发展,发展了一系列的研究计划、研究机构和战略目标,但计算方法的不足导致整个糖组学的发展缓慢。在前期工作中,我们发展了基于二级质谱的肽段的鉴定策略MS-Simulator以及初步建立了基于多级质谱的多糖结构的准确快速的鉴定方法,能够辅助实验人员快速进行多肽序列和多糖精细结构的鉴定。基于前期对肽段的研究工作MS-Simulator和基于多级质谱的多糖鉴定策略为基础,本课题拟使用一种启发式的糖肽鉴定策略,分而制之地实现多糖精细结构、肽序列、糖基化位点的鉴定,进而得到糖肽和糖蛋白的完整,精细结构,这将大大加快糖蛋白质组学的研究进展。
英文摘要
As one of the most important post-translational modifications, glycosylation has a significant effect on the structure and functions of proteins. But there is still not a high-throughput technology to watch the structures changing of the glycans and glycoproteins in cells. If this problem can be solved, it can help biologist to know functions of the glycans and its structure in cell. International efforts have been put to develop research plan for glycans, but the limitation of the computation is hindering the development of glycomics. In our previous work, we have developed a peptide identification strategy using tandem mass spectrometer, its name is MS-Simulator and a glycan identification strategy using multistage-mass spectrometer, named bigGIPS. Based on these works, we plan to develop a strategy to identify the whole glycoproteins using a divide-and-conquer approach, including identifying the branching of the glycans, the bonding site of glycans and the sequence of the peptides. Base on the this strategy, we can get the whole information of the glycopeptides and glycoproteins. This strategy will greatly speed up the development of glycomics.
