Convergent chemoenzymatic synthesis and biological evaluation of a heparan sulfate proteoglycan syndecan-1 mimetic.

A new convergent chemoenzymatic synthesis strategy, integrating enzymatic synthesis of heparan sulfate, sortase A ligation, copper(i)-catalyzed alkyne-azide cycloaddition, and solid phase peptide synthesis, has been established to efficiently synthesize a mimetic of heparan sulfate proteoglycan syndecan-1 glyco-polypeptide at a milligram scale. The mimic was able to bind with αvβ3 integrin faster and exhibit stronger inhibition of breast cancer cell migration compared to the glycan or the polypeptide alone. This novel approach could serve as a general approach for heparan sulfate proteoglycan mimetic synthesis.