Structural analysis of synthetic heparan sulfate oligosaccharides with fibroblast growth factors and heparin-binding hemagglutinin

Heparan sulfate interacts with a variety of proteins at the cell surface. These proteins are primarily attracted to the high negative charge distribution brought by sulfate, sulfamate, and carboxylate functionalities along the sugar chain. Apart from electrostatic interactions, hydrogen bonding and even hydrophobic interactions contribute to the complex formation. While additional sulfate/sulfamate groups are often tolerated as long as the main structural requirements are met, occasionally, certain extra sulfate groups may be detrimental to the binding affinity. Here, we show these binding characteristics using the binding of fibroblast growth factors and heparin-binding hemagglutinin to synthetic heparan sulfate oligosaccharides as examples. Insights into the binding characteristics of these proteins may benefit future therapeutic interventions.