Comparative analysis of fusion tags used to functionalize recombinant antibodies

Protein Expr Purif. 2020 Feb:166:105505. doi: 10.1016/j.pep.2019.105505. Epub 2019 Sep 26.

Abstract

Recombinant antibodies can be expressed as fusion constructs in combination with tags which simplify their engineering into reliable and homogeneous immunoreagents by allowing site-specific, 1:1 functionalization. Several tags and corresponding reagents for recombinant protein derivatization have been proposed but benchmarking surveys for the evaluation of their effect on the characteristics of recombinant antibodies have not been reported. In this work we evaluated the impact on expression yields, shelf-stability, thermostability and binding affinity of a set of C-terminal tags fused to the same anti-Her2 nanobody. Furthermore, we assessed the efficiency of the derivatization process. The constructs always bore a 6xHis tag plus either the controls (EGFP and C-tag) or CLIP, HALO, AviTag, the LEPTG sequence recognized by Sortase A (Sortase tag), or a free cysteine. The advantages and drawbacks of the different systems were analyzed and discussed.

Keywords: Antibody functionalization; Fusion tags; Nanobodies; Recombinant antibodies; Sortase.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding, Competitive
  • Cysteine / metabolism
  • Escherichia coli
  • Escherichia coli Proteins / chemistry
  • Escherichia coli Proteins / genetics
  • Genetic Vectors / genetics
  • Green Fluorescent Proteins / chemistry
  • Green Fluorescent Proteins / genetics
  • Oxidoreductases / chemistry
  • Oxidoreductases / genetics
  • Protein Disulfide-Isomerases / chemistry
  • Protein Disulfide-Isomerases / genetics
  • Protein Stability
  • Receptor, ErbB-2 / chemistry
  • Receptor, ErbB-2 / genetics
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics*
  • Single-Domain Antibodies / chemistry
  • Single-Domain Antibodies / genetics*

Substances

  • Escherichia coli Proteins
  • Recombinant Fusion Proteins
  • Single-Domain Antibodies
  • Green Fluorescent Proteins
  • Oxidoreductases
  • sulfhydryl oxidase
  • Receptor, ErbB-2
  • Protein Disulfide-Isomerases
  • dsbC protein, E coli
  • Cysteine