Inhibition of selectin binding by colloidal gold with functionalized shells

Area of Science:

• Biomaterials science
• Glycobiology
• Nanotechnology

Background:

• Selectins (P-selectin and L-selectin) are crucial cell adhesion molecules involved in inflammatory and immune responses.
• Understanding and modulating selectin-ligand interactions is vital for developing therapeutics for various diseases.

Purpose of the Study:

• To develop and characterize gold nanoparticles with sulfated thiol shells for targeting P- and L-selectins.
• To evaluate the binding affinity and selectivity of these nanoparticles for P- and L-selectins.

Main Methods:

• Synthesis of gold colloids functionalized with terminally sulfated thiol shells.
• Affinity assessment using IC50 values for P- and L-selectin binding.
• Comparison of binding affinities for different epitope structures, including branched acyclic epitopes and sulfated carbohydrate mimetics.

Main Results:

• Gold nanoparticles demonstrated potent binding to both P- and L-selectins, with IC50 values in the picomolar range.
• Branched acyclic epitopes displayed the highest binding affinity.
• A sulfated carbohydrate mimetic achieved the best selectivity for selectin binding.

Conclusions:

• Terminally functionalized sulfated gold nanoparticles are effective ligands for P- and L-selectins.
• Epitope design significantly influences binding affinity and selectivity, offering opportunities for targeted therapeutic strategies.