The effects of metal ions on heparin/heparin sulfate-protein interactions

Abstract

Heparin/heparin sulfate (HS) interacts with a number of proteins thereby playing an essential role in the regulation of many physiological processes. The understanding of heparin/HS-protein interactions at the molecular level is of fundamental importance to biology and will aid in the development of highly specific glycan-based therapeutic agents. The heparin-binding proteins (HBPs) interact with sulfated domains of heparin/HS chains primarily through ionic attraction between negatively charged groups in HS/heparin chains and basic amino acid residues within the protein. Reports in literature have been shown that heparin molecules have a high affinity for a wide range of metal ions. In the present study, we used surface plasmon resonance (SPR) to study the effects of metal ions (under physiological and non-physiological concentrations) on heparin/HS-protein interactions. The results showed that under non-physiological of metal ion concentration, different metal ions showed different effects on heparin binding to fibroblast growth factor-1 (FGF1) and interleakin-7 (IL7). While the effects of individual metal ion at physiological concentrations had little impact on protein binding, the mixed metal ions reduced the FGF1/heparin or IL7/heparin binding affinity, changing its binding profile.