Synthesis and in silico characterization of artificially phosphorylated glycosaminoglycans

Krzysztof Bojarski , Jana Becher , Thomas Riemer , Katharina Lemmnitzer , Stephanie Möller , Jürgen Schiller , Matthias Schnabelrauch , Sergey Samsonov


Glycosaminoglycans (GAGs) are key players in many important biologically relevant processes occurring in the extracellular matrix (ECM) thanks to their interactions with various protein targets. Chemically, GAGs represent a particular class of linear anionic polysaccharides with alternating monosaccharide units classified into several groups depending on their disaccharide unit composition and glycosidic linkage type. In addition, different sulfation patterns of these saccharides contribute to their significant heterogeneity. Recently, it was shown that chemical modifications of GAGs such as additional sulfation could lead to the attenuation of their function in biochemical processes in ECM, which is promising for applications in cell signaling, drug delivery and tissue engineering. Other potential chemical modifications for this class of molecules could be of practical significance and, therefore, should be increasingly considered in GAG research. In our work, we aimed, for the first time, to synthesize and characterize phosphorylated GAGs using experimental and computational approaches. Phosphorylation could be an attractive modification of GAGs because: (i) they would be resistant against GAG-specific glycosidases; (ii) a phosphate group could be protonated and deprotonated under physiological conditions suggesting a broader pattern of potential physicochemical properties; (iii) due to the high crosslinking ability of phosphates, related phosphorylated GAG (pGAG) hydrogels provide an interesting route to functional ECM-like structure, and potential biomaterial formulations for drug release or tissue regenerations. We report data on the synthesis of pGAGs in different reaction systems, their analytical characterization by MS and NMR approaches. Then, pGAGs as well as their monosaccharide components were systematically described by means of theoretical methods and compared to sulfated GAGs. Furthermore, we characterized the putative pGAG recognition by several well-characterized protein partners of the corresponding sulfated GAGs. Our results suggest that this novel class of molecules represents an interesting topic of GAG research despite the observed challenges in their synthetic production.
Author Krzysztof Bojarski (FCh / DTCh / LMM)
Krzysztof Bojarski,,
- Laboratory of Molecular Modeling
, Jana Becher
Jana Becher,,
, Thomas Riemer
Thomas Riemer,,
, Katharina Lemmnitzer
Katharina Lemmnitzer,,
, Stephanie Möller
Stephanie Möller,,
, Jürgen Schiller
Jürgen Schiller,,
, Matthias Schnabelrauch
Matthias Schnabelrauch,,
, Sergey Samsonov (FCh / DTCh / LMM)
Sergey Samsonov,,
- Laboratory of Molecular Modeling
Journal seriesJournal of Molecular Structure, ISSN 0022-2860, (A 20 pkt)
Issue year2019
Publication size in sheets0.75
Keywords in EnglishHyaluronan, phosphorylation, crosslinking, conformational analysis, protein-glycosaminoglycan interactions
ASJC Classification1604 Inorganic Chemistry; 1605 Organic Chemistry; 1607 Spectroscopy; 1602 Analytical Chemistry
Languageen angielski
Score (nominal)20
ScoreMinisterial score = 20.0, 05-08-2019, ArticleFromJournal
Publication indicators Scopus SNIP (Source Normalised Impact per Paper): 2016 = 0.751; WoS Impact Factor: 2017 = 2.011 (2) - 2017=1.784 (5)
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* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.