Chemoenzymatic Synthesis of Heparan Sulfate Oligosaccharides by a Covalent Catch-and-Release Approach.

A covalent catch-and-release approach is described for the chemoenzymatic synthesis of HS oligosaccharides. It exploits that a glycan modified by a hydrazide tag can under mild acidic conditions efficiently be reacted with an aldehyde-containing resin to give an immobilized hydrazone product. The hydrazone is stable under neutral conditions, allowing stringent washing conditions to remove all other components. The product can be released by transiminolysis using aqueous hydroxylamine, which, after evaporation, yields a compound that can be immediately employed in the next cycle of modification. As many as 11 consecutive transformations could be performed to give a homogenous octasaccharide having a complex pattern of sulfation and epimerization. The methodology provides opportunities to prepare convenient collections of biologically important HS oligosaccharides for structure-function studies.