A review of the thermodynamics of protein association to ligands, protein adsorption, and adsorption isotherms

The application of thermodynamic models in the development of chromatographic separation processes is discussed. The paper analyses the thermodynamic principles of protein adsorption. It can be modeled either as a reversible association between the adsorbate and the ligands or as a steady-state process where the rate of adsorption is equal to the rate of desorption. The analysis includes the competitive Langmuir isotherm and the exponentially modified Langmuir isotherm. If the adsorbate binds to one ligand only, the different approaches become identical. When the adsorbate acts as a ligand, dimerization takes place and will give rise to a sigmoid isotherm. A model that accounts for dimerization is discussed and a sample calculation shows the behavior of this isotherm. Insulin is known to have a concave isotherm at low concentrations. The calculation of the standard Gibbs energy change of adsorption is discussed. Hydrophobic and reversed phase chromatography are useful techniques for measuring solute activity coefficients at infinite dilution.

[1]  S. Cramer,et al.  Effect of pH changes on water release values in hydrophobic interaction chromatographic systems. , 2005, Journal of chromatography. A.

[2]  J. Mollerup,et al.  The thermodynamic principles of ligand binding in chromatography and biology. , 2007, Journal of biotechnology.

[3]  L. Ettre,et al.  Nomenclature for chromatography (IUPAC Recommendations 1993) , 1993 .

[4]  S. Cramer,et al.  Protein Interactions in Hydrophobic Charge Induction Chromatography (HCIC) , 2005, Biotechnology progress.

[5]  Alois Jungbauer,et al.  Whey proteins as a model system for chromatographic separation of proteins. , 2003, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[6]  Steven M. Cramer,et al.  Steric mass‐action ion exchange: Displacement profiles and induced salt gradients , 1992 .

[7]  S. Cramer,et al.  Hydrophobic displacement chromatography of proteins. , 2000, Biotechnology and bioengineering.

[8]  Tatiana Chevaldina,et al.  Thermodynamics of hydrophobic interaction chromatography of acetyl amino acid methyl esters. , 2008, Journal of chromatography. A.

[9]  Steven M Cramer,et al.  Prediction of protein retention times in gradient hydrophobic interaction chromatographic systems. , 2008, Journal of chromatography. A.

[10]  S. Cramer,et al.  Gibbs free energy of adsorption for biomolecules in ion-exchange systems. , 1994, Biophysical chemistry.

[11]  Steven M Cramer,et al.  Modeling of adsorption in hydrophobic interaction chromatography systems using a preferential interaction quadratic isotherm. , 2003, Journal of chromatography. A.

[12]  Arne Staby,et al.  Quality by design--thermodynamic modelling of chromatographic separation of proteins. , 2008, Journal of chromatography. A.

[13]  Jen Sc.  Galenics of Insulin , 1987, Springer Berlin Heidelberg.

[14]  J. Mollerup.  Applied thermodynamics: A new frontier for biotechnology , 2006 .

[15]  F. Antia,et al.  Gradient elution in non-linear preparative liquid chromatography , 1989 .

[16]  Arne Staby,et al.  Development, modelling, optimisation and scale-up of chromatographic purification of a therapeutic protein , 2007 .

[17]  C. Horváth,et al.  Retention thermodynamics in hydrophobic interaction chromatography , 1996 .

[18]  A. Rathore,et al.  Generalizing a two-conformation model for describing salt and temperature effects on protein retention and stability in hydrophobic interaction chromatography. , 2007, Journal of chromatography. A.

[19]  C. Horváth,et al.  Salt effect on hydrophobic interactions in precipitation and chromatography of proteins: an interpretation of the lyotropic series. , 1977, Archives of biochemistry and biophysics.