Protein labeling approach to improve lysosomal targeting and efficacy of antibody-drug conjugates
Ying Han1, Yifan Da1, Mingjia Yu2
1School of Pharmaceutical Sciences, Sun Yat-sen University, 132 East Outer Ring Road, Guangzhou, 510006, China. caixq7@mail.sysu.edu.cn.
Organic & Biomolecular Chemistry
|February 29, 2020
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.


