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  Investigation of Glycosaminoglycans with Ion Mobility-Mass Spectrometry and Gas-Phase IR Spectroscopy

Polewski, L. (2019). Investigation of Glycosaminoglycans with Ion Mobility-Mass Spectrometry and Gas-Phase IR Spectroscopy. Master Thesis, Freie Universität, Berlin.

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 Creators:
Polewski, Lukasz1, Author           
Pagel, Kevin1, Referee           
Schalley, Christoph A., Referee
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1Molecular Physics, Fritz Haber Institute, Max Planck Society, ou_634545              

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 Abstract: Glycosaminoglycans (GAGs) are a family of polydisperse polysaccharides, which are widely distributed at cell surfaces and in the extracellular matrix. Although structurally simple at first glance, with a repeating backbone of alternating hexuronic acid and hexosamine dimers, they display a highly complex structure, which results from their heterogeneous sulfation pattern. Even though structurally poorly understood, there has been increasing evidence that GAGs can transchelate gadolinium-based magnetic resonance imaging (MRI) contrast agents. This unintended release of gadolinium is the leading cause of nephrogenic systemic fibrosis. To date, however, the lack of structurally well-defined GAG samples has hindered a detailed elucidation of the underlying mechanism and only soft evidence of a GAG-induced gadolinium release has been reported.
In this work we demonstrate the purification and isolation of GAG fragments from low- molecular-weight-heparin (LMWH) enoxaparin using size-exclusion chromatography. Additionally, we provide the first direct evidence for GAG-gadolinium binding using the synthetic model substance fondaparinux and LMWH enoxaparin. Gas-phase IR spectroscopy and CID-MS/MS experiments revealed possible binding sites of gadolinium on fondaparinux, with surprisingly strong binding contribution from hexuronic acid site chains. This data represent the first direct insights into this complex interaction and will in the future help to unravel the molecular details of GAG-induced gadolinium transchelation from MRI contrast agents.

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Language(s): eng - English
 Dates: 2019-10-23
 Publication Status: Accepted / In Press
 Pages: XII, 55
 Publishing info: Berlin : Freie Universität
 Table of Contents: -
 Rev. Type: -
 Identifiers: -
 Degree: Master

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