Benzotriazole-5-carboxylic as a mixed-mode ligand for chromatographic separation of antibody with enhanced adsorption capacity

J Chromatogr B Analyt Technol Biomed Life Sci. 2021 Aug 1:1179:122652. doi: 10.1016/j.jchromb.2021.122652. Epub 2021 Mar 11.

Abstract

Mixed-mode chromatography provides a promising strategy for industrial protein purification for its potential merit of balancing efficiency and cost-effectiveness. However, mixed-mode media with satisfactory selectivity and binding capacity towards antibody are still urgently needed. A new type of mixed-mode chromatography resin was prepared using benzotriazole-5-carboxylicas as ligand (BTA MM), and its application in antibody separation was explored. A typical pH-dependent protein binding was observed, and the neutral condition was favorable for antibody adsorption. Dynamic binding capacity of human immunoglobulin G (hIgG) was 57.7 mg/mL at pH 7.4 (10 mM phosphate buffer, containing 150 mM NaCl), while elution with acidic solutions (pH 3-4) could achieve a recovery of more than 85%. Protein adsorption on the resin showed a salt-independent manner, thus it could work under physiological solution conditions, with satisfied antibody selectivity. One-step purification of antibody components from human serum samples could obtain a product with the purity more than 84%. Satisfied performance was also observed when the adsorbent was used for purifying a IgG1-type monoclonal antibody (mAb) from cell culture supernatant. In addition, the benzotriazole adsorbent has been found stable enough to withstand autoclave sterilization and other harsh conditions, including 1 M NaOH, 1 M HCl, and 75% ethanol. The results proved the potential of this type of mixed-mode chromatography medium for industrial antibody purification.

Keywords: Antibody purification; Benzotriazole-5-carboxylic; Ligand; Mixed-mode chromatography.

MeSH terms

  • Adsorption
  • Animals
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / isolation & purification*
  • CHO Cells
  • Chromatography, Liquid / methods*
  • Cricetinae
  • Cricetulus
  • Humans
  • Immunoglobulin G / isolation & purification
  • Ligands
  • Triazoles / chemistry*

Substances

  • Antibodies, Monoclonal
  • Immunoglobulin G
  • Ligands
  • Triazoles
  • 1H-benzotriazole-5-carboxylic acid