Utvecklande av kemiska verktyg för att effektivt detektera, karaktärisera och undersöka biologin kring glykoprotein sulfatering

Sulfation on glycoproteins plays many important biological functions.

In spite of the importance and common abundance on basically every human epithelial tissue, little scientific attention are given to explore oligosaccharide sulfation on O- and N-glycoproteins.

To enable further functional studies and detailed characterization, organic synthesis is needed to provide homogeneous glycosylated material. Glycoproteomic analysis is further important to identify and characterize these modifications. To date, applicable synthetic approaches to prepare sulfated glycopeptides are missing.

In this proposal, strategies to prepare sulfoglycopeptides will be explored. A new class of sulfate protecting groups (ArDCV) will be developed and used in Fmoc-SPPS of sulfoglycopeptides.

Enzymatic post-SPPS sulfation of glycopeptides with increasing complexity of core-structure will additionally be evaluated.

The currently available bioinformatics tools used for high-throughput glycopeptide analysis show limitations in reliable structural assignment.

Further, mass spectrometry (MS) based identification of critical glycan isomer and linkage connections have been inaccessible for determinations.

To move forward in the construction of new bioinformatics tools for glycoproteomic analysis, synthetic model glycopeptides will be used in MS-fragmentation studies to characterize unique glycopeptide isomers based on the classification of low-mass oxonium-ion ratios.