Unravelling Glycochemistry with Ion Mobility Spectrometry and Gas-Phase Spectroscopy

Projektbeschreibung

Der süße Geschmack des Erfolgs: Grundlagen der Glykomik erforschen

Glykane sind komplexe Zucker, die aus drei oder mehr Monosacchariden, wie etwa Glukose, bestehen und auf komplexe Weise miteinander verbunden sind. Sie gehören zu den vielfältigsten und wichtigsten Verbindungen in der Natur. Ob eigenständig oder an Proteine (Glykoproteine), Lipide (Glykolipide) und andere Moleküle gebunden, Glykane spielen eine zentrale Rolle in unserem Körper. Dazu gehören die Zellerkennung und die Signalübertragung, die Auswirkungen auf den Stoffwechsel, Entzündungen und das Immunsystem haben. Die strukturelle Vielfalt der Glykane stellt eine grundlegende Herausforderung sowohl für ihre chemische Synthese als auch für ihre Charakterisierung dar. Das EU-finanzierte Projekt GlycoSpec wird die Glykochemie und ihre vielfältigen Mechanismen entschlüsseln, um den Weg für die Glykomik und die breite Verfügbarkeit von Oligosacchariden für sozioökonomisch wichtige Anwendungen zu ebnen.

Ziel

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.