Pegylated species separation through an innovative PEG-grafted agarose-based resin, association quantified by microcalorimetry Academic Article in Scopus uri icon

abstract

  • © 2020 Elsevier B.V.The study of thermodynamic parameters of hydrophobic interaction chromatography (HIC) leads to a better understanding of protein-stationary phase interactions to design and validate new separation systems. In previous works, we have developed an innovative polyethylene(glycol) (PEG)-grafted resin, which was highly efficient in the separation of PEGylated ribonuclease A (RNase A) species in a single step. Moreover, we have described its electrokinetic profile. However, new platforms for other proteins need to be developed and microcalorimetric analysis needs to be performed. The aim of this work was to design a new platform for lysozyme PEGylated species separation using the PEG-grafted resin, and to quantify the changes of energy caused by reversible interactions between the PEG-grafted resin and PEGylated proteins (RNase A and lysozyme) by isothermal titration calorimetry (ITC). The grafted resin and the PEGylated proteins were characterized by ATR-FTIR. Titrations were carried out in potassium phosphate buffer with 1.5 M ammonium sulfate at 25 °C. ATR-FTIR spectra demonstrated the chemical modification of the resin. Resolution of native from mono-PEGylated lysozyme was 0.93 whereas resolution of mono-PEGylated from di-PEGylated form was 1.92. The specific enthalpy was exothermic for both proteins. Mono-PEGylated proteins had a negative entropy, related to the enhanced hydrophobic interaction between PEG5000 molecules from the resin and PEGylated proteins.

publication date

  • December 15, 2020