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Keywords:

  • allyl groups;
  • biotinylation;
  • click chemistry;
  • lactose;
  • protecting groups;
  • structure–activity relationships

Abstract

Chondroitin sulfate-E (CS-E) oligosaccharidic analogues (di to hexa) were prepared from lactose. In these compounds, the 2-acetamido group was replaced by a hydroxyl group. This modification speeded up the synthesis, and large oligosaccharides were constructed in a few steps from a lactose-originated block. The protecting groups used were as follows; Fmoc for hydroxyl groups to be glycosylated, allyl group for anomeric position protection, and trichoroacetimidate leaving groups were used to prepare up to octasaccharides. We took advantage of the presence of allyl group to develop a click biotinylation, through its transformation into a 3-azido-2-hydroxyl propyl group in two steps (epoxidation and sodium azide epoxide opening). The biotinylating agent was a water-soluble propargylated and biotinylated triethylene glycol (PEG). By using surface plasmon resonance (SPR), it was shown that the di-, tetra-, and hexasaccharides display a binding affinity and selectivity toward HSF/GSF and CXCL12 similar to that of CS-E. A parallel study confirmed their mimicry of natural compounds, based on the hexasaccharide interaction with Otx2, a homeodomain protein involved in brain maturation, thus validating our simplification approach to synthesize bioactive GAG.