The interaction between human serum albumin and antidiabetic agent - exenatide: determination of the mechanism binding and effect on the protein conformation by fluorescence and circular dichroism techniques - Part I.

The interactions between transport proteins and drugs are very important from the pharmacological point of view. In this study, using fluorescence and circular dichroism (CD) techniques, we investigated the interaction between human serum albumin (HSA) and incretin antidiabetic drug - exenatide. Moreover, the effect of common metal ions (Ca, Zn, Cr) on the exenatide-HSA binding - was also described. Based on the experimental data under pseudophysiological conditions, the calculated binding constant values are on the order of 10 M, and the constants are lower in the presence of metal ions. We observed the increase of the hydrophobicity near the tryptophan-214 residue in subdomain IIA, but almost no change in the hydrophobicity surrounding tyrosine residues. A similar effect on the tryptophan microenvironment is influenced by metal ions. The calculated thermodynamic parameters indicated that the characteristic electrostatic and hydrophobic interactions play an important role in the albumin-exenatide complexes. The CD studies showed that exenatide does not change the secondary structure of the protein but used metal ions have some impact on albumin α-helical content.Communicated by Ramaswamy H. Sarma.