Field of Drug Discovery Research, Faculty of Advanced Life Science, Hokkaido University, Kita-ku, Sapporo, Japan.
Adv Carbohydr Chem Biochem. 2011;65:219-71. doi: 10.1016/B978-0-12-385520-6.00005-4.
As drastic structural changes in cell-surface glycans of glycoproteins and glycosphingolipids, as well as serum glycoproteins, are often observed during cell differentiation and cancer progression, it is considered that glycans can be potential candidates for novel diagnostic and therapeutic biomarkers. Although there have been substantial advances in our understanding of the effects of glycosylation on some biological systems, we still do not fully understand the significance and mechanism of glycoform alteration that is widely observed in many human diseases. This is due to the highly complicated structures of the glycans and the extremely tedious and time-consuming processes required for their separation from complex mixtures and their subsequent analysis. As a result, with a few notable exceptions, the therapeutic potential of complex glycans has not been well exploited. This article is focused on the state of the art and current advances in glycomics, and efforts for the development of automated glycan analysis, which should greatly accelerate functional glycobiology and its medical/pharmaceutical applications. The "glycoblotting method" is the only method currently available that allows rapid and large-scale clinical glycomics of human whole-serum glycoproteins, because it requires very little material and, when combined with an automated system "SweetBlot," takes only ∼14h to complete whole glycan profiling by mass spectrometry. The upcoming goal is to combine glycoblotting methods and various MS-based platforms for the development of a fully automated glycan analytical system and accelerating research to discover highly sensitive and clinically important biomarker molecules.
由于细胞表面糖蛋白和糖脂以及血清糖蛋白的结构发生剧烈变化，通常在细胞分化和癌症进展过程中观察到，因此糖链被认为是潜在的候选新型诊断和治疗生物标志物。尽管我们对糖基化对某些生物系统的影响有了实质性的了解，但我们仍然不完全了解在许多人类疾病中广泛观察到的糖型改变的意义和机制。这是由于聚糖的高度复杂结构以及从复杂混合物中分离和随后分析所需的极其繁琐和耗时的过程。因此，除了少数几个显著的例外，复杂聚糖的治疗潜力尚未得到充分开发。本文重点介绍糖组学的最新技术和进展，以及开发自动化聚糖分析的努力，这将极大地加速功能糖生物学及其在医学/药物方面的应用。“糖印迹法”是目前唯一可用于快速大规模临床检测人全血清糖蛋白的方法，因为它所需的材料非常少，当与自动化系统“SweetBlot”结合使用时，只需约 14 小时即可通过质谱完成全聚糖分析。即将到来的目标是将糖印迹方法与各种基于 MS 的平台相结合，开发出全自动的聚糖分析系统，并加速研究以发现高度敏感和具有临床重要性的生物标志物分子。
