Inhibition of ligand–protein complex isomerization by some dopamine transporter inhibitors

Abstract

Kinetic analysis of the interaction of four N­substituted nortropane derivatives with the dopamine transporter was made to characterize the mechanism of the binding process. The kinetics were studied by radioligand binding experiments. It was found that the studied compounds initiate a slow isomerization process of the initially formed ligand–transporter complex, but at higher concentrations, the same compounds inhibit the isomerization process. The results suggest that the studied ligands interact with two distinct binding sites of the transporter protein that have different ligand binding specificities. The interaction of ligands with different binding sites must be taken into consideration when analyzing the ligand recognition patterns of the transporter protein.

Keywords

• biokinetics
• dopamine transporter
• dat
• tropane derivatives
• ligand binding kinetics
• isomerization of ligand–protein complex