Abstract
High amounts of glycosaminoglycans (GAG) such as hyaluronan (HA) occur in connective tissues. There is nowadays increasing evidence that a "sulfation code" exists which mediates numerous GAG functions. High molecular weight and inhomogeneity of GAG, however, aggravated detailed studies. Thus, synthetic oligosaccharides were urgently required. We will review here chemoenzymatic and analytic strategies to provide defined sulfated and anomerically modified GAG oligosaccharides of the HA type. Representative studies of protein/GAG interactions by (bio)chemical and biophysical methods are reported yielding novel insights into GAG-protein binding. Finally, the biological conclusions and in vivo applications of defined sulfated GAG oligosaccharides will be discussed.
Highlights
Life expectancy and, the number of patients suffering from many different diseases and delayed healing is continuously increasing
Beyond heparins, which were introduced as potent anti-coagulants several decades ago, for a long time the knowledge of protein-GAG interactions has been limited and it took decades to discover how common GAG binding is among the proteins of the extracellular matrix
For cases in which the anomeric 1,2,3-triazole or the use of copper was not acceptable, we developed the first synthesis of unprotected 1-thio-glycosides enabling an alternative click reaction for GAG (Figure 1(c)) (Köhling et al 2016b)
Summary
The number of patients suffering from many different diseases and delayed healing is continuously increasing. Beyond heparins, which were introduced as potent anti-coagulants several decades ago, for a long time the knowledge of protein-GAG interactions has been limited and it took decades to discover how common GAG binding is among the proteins of the extracellular matrix. These discoveries have raised the interest in synthetically modified sulfated GAG oligomers as such molecules can be valuable as chemical tools for studying and understanding the functional relevance, the structural biology, and the future application potential of GAG-protein interactions. (Köhling et al 2016b) for HA4, and with chemical methods that allow the conversion of unprotected sugars into anomerically modified GAG oligosaccharides
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