Descrizione del progetto
Il dolce gusto del successo: porre le basi per la glicomica
I glicani sono zuccheri complessi costituiti da tre o più monosaccaridi, come il glucosio, collegati tra loro in modo complesso. Sono tra i composti più diversi e importanti in natura. Sia da soli che collegati a proteine (glicoproteine), lipidi (glicolipidi) e altre molecole, i glicani svolgono ruoli essenziali nel corpo. Tra questi, il riconoscimento e la segnalazione cellulare sono fondamentali, esercitando effetti sul metabolismo, sull’infiammazione e sul sistema immunitario. La diversità strutturale dei glicani pone una sfida fondamentale sia per la loro sintesi chimica che per la loro caratterizzazione. Il progetto GlycoSpec, finanziato dall’UE, svelerà la glicochimica e i suoi diversi meccanismi per aprire la strada alla glicomica e all’ampia accessibilità agli oligosaccaridi per applicazioni importanti dal punto di vista socioeconomico.
Obiettivo
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.
Campo scientifico
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-COG - Consolidator GrantIstituzione ospitante
14195 Berlin
Germania