Glycosaminoglycans are complex oligosaccharides that play diverse roles in biology. Heparan sulfate (HS) binds to multiple proteins regulating cell proliferation/differentiation signalling pathways and is involved in cancer development, pathogenic infections, and Alzheimer’s disease. The structural requirements for protein binding remain ill-defined in many cases, with regards to sulfation patterns, binding sequence lengths, and details of binding site interactions. Synthetic structurally defined HS oligosaccharides are critical to define any specific structural features related to length and sulfation pattern of synthetic HS oligosaccharides, both of which affect HS-protein interactions. Future developments in GAG-chemical biology are reliant on adding to the structural arrays available and the development of new methods used to interrogate interactions. Here, we describe applications of a [2.2.2] L-ido lactone for chemoselective glycosylations, enabled through its high acceptor efficiency and remarkable donor inactivity. This unit enables synthesis of HS, and also the lesser studied DS, oligosaccharide fragments through an iterative extension strategy providing each resulting oligosaccharide fragment with a latent thioglycoside at the reducing terminus. This terminus group can be trivially reactivated as a donor through lactone opening, to further extend the oligosaccharide chain or to functionalize the reducing terminus by glycosylation with a suitable acceptor. Such functionalisation is applicable to various end groups suitable for further conjugation of immobilisation applications. This poster will review application to fluorescently labelled HS fragments and report on advances for applications to other end conjugation strategies.

Synthesis of heparan sulfate fragments and their potential conjugate applications

ACS Fall 2021

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