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 alpha v beta 3 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.

Automated summary

A novel convergent chemoenzymatic synthesis strategy has been established to efficiently synthesize a mimic of heparan sulfate proteoglycan syndecan-1, which showed enhanced binding with alpha v beta 3 integrin and stronger inhibition of breast cancer cell migration compared to individual components. This approach could serve as a general method for synthesizing heparan sulfate proteoglycan mimetics.