Toward automated glycan analysis

Abstract

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.