Utilization of Selenocysteine for Site-Specific Antibody Conjugation

Methods Mol Biol. 2017:1575:145-164. doi: 10.1007/978-1-4939-6857-2_8.

Abstract

Site-specific conjugation methods are becoming increasingly important in building next-generation antibody-drug conjugates. We have developed a site-specific conjugation technology based on monoclonal antibodies with engineered selenocysteine (Sec) residues, named selenomabs. Here, we provide protocols for the engineering, expression, and purification of selenomabs in single-chain variable fragment (scFv)-Fc format. Methods for selective conjugation of selenomabs to selenol-reactive compounds and analytical characterization of selenomab conjugates are also included.

Keywords: Antibody-drug conjugates; Selenocysteine; Selenomab; Site-specific conjugation.

MeSH terms

  • Antibodies, Monoclonal / genetics*
  • Antibodies, Monoclonal / metabolism
  • Base Sequence
  • HEK293 Cells
  • Humans
  • Immunoconjugates / genetics
  • Immunoconjugates / isolation & purification
  • Immunoconjugates / metabolism*
  • Protein Engineering
  • Selenocysteine / chemistry
  • Selenocysteine / metabolism*
  • Single-Chain Antibodies / isolation & purification

Substances

  • Antibodies, Monoclonal
  • Immunoconjugates
  • Single-Chain Antibodies
  • Selenocysteine