Modelling and Characterization of the Sorption of Kynurenic Acid on Protein Surfaces

Edit Csapó,Imre Dékány,László Vécsei,Ádám Juhász

doi:10.3311/ppch.10185

Abstract

This paper presents a surface plasmon resonance (SPR) spectroscopy-based evaluation process which provides information on kinetic and thermodynamic aspects of the interactions between proteins and a drug molecule. Reversible binding of kynurenic acid (KYNA) on human (HSA) and bovine (BSA) serum albumin-modified gold sensor surface has been investigated under physiological conditions at various temperatures. The SPR sensorgrams were fitted via nonlinear parameter estimation method by using pseudo first order kinetic model. Based on the concentration dependence of the estimated observed rate constants (kobs ) the association (ka ) and dissociation (kd ) constants as well as the equilibrium constants (KA ) and the Gibbs free energy (ΔG0) change were calculated at different (10-35 C°) temperatures. Furthermore, the enthalpy (ΔH0), entropy (ΔS0) and heat capacity changes (ΔCp ) of KYNA-protein complex formation were also calculated.

Highlights

For protein-based controlled drug delivery and drug release systems the study of the interactions between the protein as the carrier and a drug molecule play a determinant role in pharmaceutical developments [1, 2]
This paper presents a surface plasmon resonance (SPR) spectroscopy-based evaluation process which provides information on kinetic and thermodynamic aspects of the interactions between proteins and a drug molecule
For calculations of the kinetics parameters the A+B↔AB type bimolecular reaction model was used, where A corresponds to the drug molecule, B is the protein, while AB is the kynurenic acid (KYNA)-serum albumin complex

Summary

Introduction

For protein-based controlled drug delivery and drug release systems the study of the interactions between the protein as the carrier and a drug molecule play a determinant role in pharmaceutical developments [1, 2]. The SPR spectroscopy is one of the most useful quasi two-dimensional technique which is able to measure real-time association and dissociation processes between DNA–DNA, DNA–protein, lipid–protein and protein- or peptides–drug molecules in a label free environment [3,4]. While one of the interacting partners is immobilized onto the sensor surface, the other is flow in solution over the surface or exist as bound (surface complex) form. During this progression, the refractive index at the interface undergoes change, this being directly related to the amount of the biomolecules adsorbed on the surface of the biosensor chip

Objectives

Methods

Results

Conclusion