Protein labeling approach to improve lysosomal targeting and efficacy of antibody–drug conjugates
Ying Han, Yifan Da, Mingjia Yu, Yaping Cheng, Xin Wang, Jiale Xiong, Guoying Guo, Yan Li, Xianxing Jiang, Xiaoqing Cai
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.
Topics & Concepts
LysosomeEndocytosisConjugateChemistryEndosomeSortaseClathrinAntibodyDrugLigationBiochemistryCell biologyMolecular biologyBiologyPharmacologyImmunologyGeneReceptorBacterial proteinEnzymeMathematical analysisMathematicsBiochemical and Structural CharacterizationCellular transport and secretionGlycosylation and Glycoproteins Research