Sequential dual site-selective protein labelling enabled by lysine modification

Bioorg Med Chem. 2020 Nov 15;28(22):115783. doi: 10.1016/j.bmc.2020.115783. Epub 2020 Sep 24.

Abstract

Methods that allow for chemical site-selective dual protein modification are scarce. Here, we provide proof-of-concept for the orthogonality and compatibility of a method for regioselective lysine modification with strategies for protein modification at cysteine and genetically encoded ketone-tagged amino acids. This sequential, orthogonal approach was applied to albumin and a therapeutic antibody to create functional dual site-selectively labelled proteins.

Keywords: Albumin; Antibodies; Bioorthogonal labelling; Lysine modification; Protein modification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albumins / chemistry
  • Albumins / metabolism*
  • Antibodies / chemistry
  • Antibodies / metabolism*
  • Lysine / chemistry
  • Lysine / metabolism*
  • Molecular Structure
  • Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / chemistry
  • Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / metabolism

Substances

  • Albumins
  • Antibodies
  • Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase
  • Lysine