Simplified in vitro refolding and purification of recombinant human granulocyte colony stimulating factor using protein folding cation exchange chromatography

J Chromatogr A. 2015 Jan 30:1379:74-82. doi: 10.1016/j.chroma.2014.12.057. Epub 2014 Dec 29.

Abstract

Protein folding-strong cation exchange chromatography (PF-SCX) has been employed for efficient refolding with simultaneous purification of recombinant human granulocyte colony stimulating factor (rhG-CSF). To acquire a soluble form of renatured and purified rhG-CSF, various chromatographic conditions, including the mobile phase composition and pH was evaluated. Additionally, the effects of additives such as urea, amino acids, polyols, sugars, oxidizing agents and their amalgamations were also investigated. Under the optimal conditions, rhG-CSF was efficaciously solubilized, refolded and simultaneously purified by SCX in a single step. The experimental results using ribose (2.0M) and arginine (0.6M) combination were found to be satisfactory with mass yield, purity and specific activity of 71%, ≥99% and 2.6×10(8)IU/mg respectively. Through this investigation, we concluded that the SCX refolding method was more efficient than conventional methods which has immense potential for the large-scale production of purified rhG-CSF.

Keywords: Cation exchange chromatography; Mass yield; PFLC; Purity; Specific activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cations / chemistry
  • Chromatography*
  • Escherichia coli / chemistry
  • Granulocyte Colony-Stimulating Factor / chemistry*
  • Granulocyte Colony-Stimulating Factor / isolation & purification
  • Humans
  • In Vitro Techniques
  • Molecular Weight
  • Protein Folding
  • Recombinant Proteins / chemistry*
  • Urea / chemistry

Substances

  • Cations
  • Recombinant Proteins
  • Granulocyte Colony-Stimulating Factor
  • Urea