Glycans, also known as oligosaccharides or polysaccharides, are polymers consisting of individual sugar molecules (i.e. monosaccharides) linked to one another. They are ubiquitous in nature and represent one of the most important classes of molecules in living systems. Nearly every cell is coated with a layer of glycans that plays a central role in cell-to-cell communication, the recognition of pathogens, and the transport of molecules into the cell. As a result, they are involved in one way or another in virtually every human disease.
Glycans are central to the functioning of biotherapeutics, for example. The pattern of glycans attached to a protein drug affects its effectiveness, lifetime, and cytotoxicity, and this must be carefully controlled during their biosynthesis. Viruses often use glycans to shield themselves from detection, making analysis of the glycans coating the viral surface a key step in developing effective vaccines. Changes in the glycans attached to proteins are often associated with certain diseases, and thus they can be used as biomarkers for early disease detection. Free glycans found in human milk play an important role in the immune development of infants.
Given the undeniable importance of glycans, one needs a fast and reliable way to detect and analyze them, akin to the powerful tools used for protein analysis. The problem is that glycans are notoriously difficult to analyze. Because many of the monosaccharide building blocks have the same mass (i.e. they are isomers), glycans with different monosaccharide content can also be isomeric and thus cannot easily be distinguished by mass spectrometry, which is the most sensitive tool used for biomolecular analysis. In addition, there are a variety of ways that the building blocks can be connected to one another, giving rise to an additional level of isomeric complexity.
The goal of the GLYCANAL project has therefore been to develop a completely new approach to glycan analysis that is sensitive, fast, and accurate. The approach that we have taken has been to measure the manner in which each molecule absorbs infrared radiation, which provides a unique, identifying fingerprint of the molecule, and we do this in combination with ultrahigh-resolution ion mobility selection of different isomers, which first sorts them by their shape. These measurements are made inside a mass spectrometer, which makes them extremely sensitive.
The ultimate objectives are: (1) to develop an extensive spectroscopic database for glycan isomers that can be used to identify them rapidly; and (2) to make this technique widely available to researchers in companies and academia.
