Double labelling to facilitate the study of glycosaminoglycans

Heparan sulfate (HS) are sulfated polysaccharides of the Glycosaminoglycans family that participate in many cellular processes because of their ability to interact and modulate a wide range of signalling proteins. These interactions involve particular HS motifs, defined by their saccharide sequence and sulfation profile. However, the structural features of these functional domains remain mostly unknown, due to the molecular complexity of these polysaccharides and a lack of tools dedicated to their analysis.

In this context, the researchers of the SAGAGAG group, in collaboration with the Parisian Institute of Molecular Chemistry and the LG2A laboratory in Amiens, have developed a method allowing a double labelling of HS oligosaccharides, using Thia-Michael type addition and deuterium incorporation, respectively at the non-reducing and reducing ends of the sugar. This new labelling technique allows the combination of microgram-scale oligosaccharide labelling and mass spectrometric analysis, without altering HS/protein recognition properties, as demonstrated for heparinase I and HSulf-2 enzymes. This method is a new tool that should allow new developments for the sequencing of GAG oligosaccharides and the elucidation of new structure/function relationships.

A microscale double labelling of GAG oligosaccharides compatible with enzymatic treatment and mass spectrometry. Przybylski C, Bonnet V, Vivès RR. Chemical Communications; 55(29):4182-4185.