Project description
The sweet taste of success: Laying the foundations for glycomics
Glycans are complex sugars consisting of three or more monosaccharides, like glucose, linked together in a complex fashion. They are among the most diverse and important compounds in nature. Whether stand-alone or attached to proteins (glycoproteins), lipids (glycolipids) and other molecules, glycans play essential roles in the body. Among them, cell recognition and signalling are key with effects on metabolism, inflammation and the immune system. The structural diversity of glycans poses a fundamental challenge for both their chemical synthesis as well as their characterisation. The EU-funded GlycoSpec project will unravel glycochemistry and its diverse mechanisms to pave the way to glycomics and broad accessibility to oligosaccharides for socioeconomically important applications.
Objective
Oligosaccharides or glycans are essential in nature and central participants in virtually every biological process. The extensive structural diversity enables glycans to encode rich information in biological functions; however, it also creates major challenges in almost all aspects of the glycosciences. The synthetic formation of glycosidic bonds during glycan assembly for example, is mechanistically still not fully understood. This is largely a result of highly-reactive, but short-lived oxocarbenium ion intermediates, which are difficult to study using established techniques. However, the structure of these intermediates dictates the stereochemistry of the resulting glycosidic bond, the control of which is absolutely crucial for a successful synthesis. An equally important aspect is the sequencing of glycans, which is generally complicated by the frequent occurrence of isomers. This is further complicated by poorly understood rearrangement reactions during mass spectrometric analysis, which often lead to erroneous structural assignments. Here as well, cationic intermediates are the key species that determine the outcome of the rearrangement.
The aim of GlycoSpec is to unravel fundamental aspects of oligosaccharide reaction and fragmentation mechanisms by probing cationic glycan intermediates. To do so, a unique combination of instrument and method development (ion mobility-mass spectrometry and cold-ion spectroscopy), chemical synthesis and theory will be used. The gain in mechanistic understanding will provide the basis to tailor building blocks and reaction conditions and is expected to lead to a major advancement in glycosynthesis. The mechanistic understanding of fragmentation reactions will furthermore lead to general rules for the prediction of tandem mass spectra. Just like in the early years of proteomics, this will make the technology automatable and accessible for broader applications. Therefore, GlycoSpec will help to initiate the pursuit of glycomics.
Fields of science
Programme(s)
Funding Scheme
ERC-COG - Consolidator GrantHost institution
14195 Berlin
Germany