Abstract
Glycosaminoglycans (GAGs) are a physio- and pharmacologically highly relevant class of complex saccharides, possessing a linear sequence and strongly acidic character. Their repetitive linear core makes them seem structurally simple at first glance, yet differences in sulfation and epimerization lead to an enormous structural diversity with only a few GAGs having been successfully characterized to date. Recent infrared action spectroscopic experiments on sulfated mono- and disaccharide ions show great promise. Here, we assess the potential of two types of gas-phase action spectroscopy approaches in the range from 1000 to 1800 cm−1 for the structural analysis of complex GAG oligosaccharides. Synthetic tetra- and pentasaccharides were chosen as model compounds for this benchmark study. Utilizing infrared multiple photon dissociation action spectroscopy at room temperature, diagnostic bands are largely unresolved. In contrast, cryogenic infrared action spectroscopy of ions trapped in helium nanodroplets yields resolved infrared spectra with diagnostic features for monosaccharide composition and sulfation pattern. The analysis of GAGs could therefore significantly benefit from expanding the conventional MS-based toolkit with gas-phase cryogenic IR spectroscopy.Graphical abstract
Highlights
Living systems encode information and function in the sequence of biopolymers
Most specific for the investigated ions are the positons of bands above 1600 cm−1, a region that is typically attributed to the stretching vibrations of carbonyl and carboxylate functional groups
The [fondaparinux+2H]2+ ion exhibits a strong absorption centered at 1755 cm−1, which indicates that two protons are located at the carboxyl functional groups, making them neutral
Summary
Determining the primary structure of nucleic acids and proteins has played a central role in the progress in life sciences, with an arsenal of sensitive and automated sequencing strategies currently available. Parts of this work were presented at ANAKON 2019, Münster (Germany) in March 2019, and have been awarded with an ABC Best Poster Award. GAGs are ubiquitous in the extracellular matrix and on cell surfaces [4]. Both as glycoconjugates and in unconjugated form, they mediate various physio- and pathophysiological processes, such as haemostasis, inflammation, tumorigenesis or target-cell recognition in infections [5, 6]. Due to its unfavorable pharmacokinetic properties, natural heparin is being increasingly substituted by low molecular weight heparins (LMWHs) and synthetic GAG analogues. The best example of the latter approach is fondaparinux (Arixtra®), a heparinrelated fully synthetic pentasaccharide, approved by the EMA and the FDA (Fig. 1a)
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