Simultaneous metal chelate affinity purification and endotoxin clearance of recombinant antibody fragments

J Immunol Methods. 2006 Jul 31;314(1-2):67-73. doi: 10.1016/j.jim.2006.05.012. Epub 2006 Jun 22.

Abstract

Endotoxins are frequent contaminants of recombinant proteins produced in Escherichia coli. Due to their adverse effects, endotoxins have to be removed from recombinant proteins prior their use in cell-based assays or parenteral application. Reduction of endotoxin to less than 10 EU mg(-1) is, however, one of the most problematic steps during protein purification from E. coli and often associated with substantial loss of biological materials. The present paper describes the use of a single step procedure enabling metal chelate affinity purification and endotoxin clearance from antibody fragments produced in E. coli using a non-ionic detergent. Endotoxin content was as low as 5 to 9 EU mg(-1) with a recovery of antibody fragments of over 90%. Non-ionic detergent treatment did not compromise integrity and functionality of these multimeric molecules. Furthermore, recombinant antibody fragments did not stimulate endotoxin-sensitive cell lines confirming the low endotoxin content. In conclusion, this one-step protocol is a rapid, cost effective and automation-compatible procedure suitable for recombinant antibody fragments.

Publication types

  • Evaluation Study

MeSH terms

  • Antibodies, Monoclonal / chemistry
  • Binding Sites, Antibody
  • Cell Line, Tumor
  • Chromatography, Affinity / methods*
  • Detergents / chemistry
  • Dimerization
  • Endothelial Cells / physiology
  • Endotoxins / chemistry*
  • Endotoxins / isolation & purification
  • Escherichia coli
  • Humans
  • Immunoglobulin Fragments / chemistry*
  • Intercellular Adhesion Molecule-1 / immunology
  • Metals*
  • Models, Molecular
  • Octoxynol
  • Polyethylene Glycols / chemistry

Substances

  • Antibodies, Monoclonal
  • Detergents
  • Endotoxins
  • Immunoglobulin Fragments
  • Metals
  • Intercellular Adhesion Molecule-1
  • Polyethylene Glycols
  • Octoxynol
  • Nonidet P-40