Research in glycomics and glycoproteomics is making rapid progress as a result of technological advances in mass spectrometry. Bioinformatics is an indispensable discipline for analyzing overwhelming amounts of information generated by mass spectrometry. This minireview summarizes bioinformatics contributions to glycan mass spectrometry data analysis. To simplify the discussion on the wide range of bioinformatics contributions to this field, the research shown here will be categorized into three areas; “Calculator-type tools,” “Technologies for glycan structure determination by tandem MS” and “Other noteworthy bioinformatics technologies for MS.” Lastly, future prospects of the contribution of bioinformatics to glycobiology will be discussed.
Heparin and heparan sulfate (HS) are complex polysaccharides that mediate and modulate the activity of numerous proteins. These proteins associate with the sugar's repeating disaccharide backbone, which is decorated with diverse sulfation patterns. Knowledge of the molecular details of these interactions may allow the development of new forms of diagnostic and therapeutic agents. Chemical syntheses of heparin- and HS-based oligosaccharides are vital in accessing the well-defined materials required by structure–activity relationship evaluations. These synthetic efforts, however, are confronted with several challenges such as access to the rare L-idose/L-iduronic acid derivatives, α-stereoselectivity in glucosaminylation, the manner of chain elongation, the selection and manipulation of protecting groups including the introduction of sulfonate groups at defined positions, and the efficient generation of compounds that are diverse enough to represent the natural heparin and HS chains. This review focuses on our achievements in addressing these concerns together with concise descriptions of the collective solutions that have been developed thus far. We also briefly highlight the results of biological assays involving our sugar constructs.
Gangliosides are major components of highly organized membrane microdomains or rafts, yet little is known about the role of gangliosides in raft organization. This is also the case of gangliosides in T cell development and activation. Primary CD4+ T cells and CD8+ T cells preferentially express differential series of gangliosides: the former a-series and the later o-series. Consistent with this, a-series and o-series ganglioside deficiency results in CD4+ and CD8+ T cell dysfunction, respectively. Ganglioside GM3 synthase deficiency, which leads to the lack of a-series gangliosides, ameliorates CD4+ T cell-mediated airway hypersensitivity in a mouse model of allergic asthma. It is therefore suggested that a variety of rafts with different gangliosides are formed on the plasma membrane of CD4+ and CD8+ T cells, which defines the immune function of individual T cell subsets. This review focuses on the selective role of different gangliosides expressed in individual T cell subsets.
The Fibroblast growth factor (FGF) is responsible for a wide range of bioactivities. Human FGF19 (hFGF19) is expressed in the ileum in response to bile acid, and after secretion into the circulation, it reaches its target organ, the liver, via the portal vein. In the liver, hFGF19 regulates bile acid synthesis. hFGF19 is an endocrine metabolic regulator. Earlier studies have suggested that hFGF19 signals through human FGF receptor 4 (hFGFR4) in the presence of a co-receptor, human βKlotho (hKLB), but its activity and receptor specificity at blood concentrations remain unclear. We explored the components to determine the liver-specific activity of hFGF19 at blood levels. The results suggested that at blood levels, hFGF19 requires sulfated glycosaminoglycans for its signaling via hFGFR4 in the presence of a co-receptor, hKLB, thus establishing specific targeting.