Efficient and Selective Bioconjugation Using Surfactants

Bioconjug Chem. 2018 Nov 21;29(11):3667-3676. doi: 10.1021/acs.bioconjchem.8b00594. Epub 2018 Oct 23.

Abstract

The surfactant sodium decanote is used in the drug substance process of Besponsa, an antibody drug conjugate (ADC), to facilitate bioconjugation between activated calicheamicin derivative (linker payload) and inotuzumab (monoclonal antibody). Under the normal conjugation process conditions, sodium decanoate forms micelles and the micelle formation was shown to be critical for the efficient conjugation reaction. Further screening studies indicated that sodium dodecyl sulfate, sodium deoxycholate, and dodecyltrimethylammonium bromide were also able to facilitate the conjugation reaction. While the choice of surfactant and its concentration in the reaction impact the conjugation efficiency, the charge of surfactant and the choice of linker payload influence the conjugated lysine site selectivity. Eight major conjugated lysine sites are observed in Besponsa, as compared to approximately 80 conjugated lysine sites typically observed in conventional lysine-based ADCs.

MeSH terms

  • Aminoglycosides / chemistry
  • Antibodies, Monoclonal, Humanized / chemistry*
  • Immunoconjugates / chemistry*
  • Inotuzumab Ozogamicin
  • Micelles
  • Peptide Mapping
  • Surface-Active Agents / chemistry*

Substances

  • Aminoglycosides
  • Antibodies, Monoclonal, Humanized
  • Immunoconjugates
  • Micelles
  • Surface-Active Agents
  • Inotuzumab Ozogamicin