Protein labeling approach to improve lysosomal targeting and efficacy of antibody-drug conjugates

Org Biomol Chem. 2020 May 6;18(17):3229-3233. doi: 10.1039/d0ob00265h.

Abstract

An anti-EGFR nanobody was labeled at the C-terminus with a lysosome-sorting NPGY (Asn-Pro-Gly-Tyr) motif via sortase-mediated ligation to enhance the engagement of the clathrin-mediated endocytosis. The synergistic effects of NPGY motif and nona-arginine peptide were found to induce robust internalization and lysosomal trafficking, which in turn improved anti-tumor activity of an antibody-drug conjugate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antibodies / chemistry*
  • Antibodies / pharmacology
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Clathrin / metabolism
  • Endocytosis / drug effects
  • ErbB Receptors / metabolism
  • Humans
  • Immunoconjugates / chemistry*
  • Immunoconjugates / pharmacology
  • Lysosomes / metabolism*
  • Molecular Conformation
  • Molecular Targeted Therapy
  • Optical Imaging
  • Peptides / chemistry*
  • Peptides / metabolism
  • Protein Binding
  • Protein Transport / drug effects

Substances

  • Antibodies
  • Antineoplastic Agents
  • Clathrin
  • Immunoconjugates
  • Peptides
  • ErbB Receptors