Precision chemical synthesis of PEGylated IGF2 for potent and selective lysosomal degradation of transmembrane proteins.

Authors

Boyuan Fan, Xiaoxiong Wei, Weijie Li, Siyi Cui, Xiaojun Wang, Jibin Cui, Yicheng Weng, Wei Cong, Man Pan, Qingyun Zheng, Qian Qu, Yuanyuan Yu

Published in

Organic & biomolecular chemistry. Jul 09, 2026. Epub Jul 09, 2026.

Abstract

We report a site-specific PEGylation strategy to stabilize insulin-like growth factor 2 (IGF2) as a functional ligand for insulin-like growth factor 2 receptor (IGF2R)-based lysosome-targeting chimera (LYTAC) systems. This chemical modification improves ligand folding and solubility, enabling efficient LYTAC-mediated epidermal growth factor receptor (EGFR) degradation across multiple cell lines and significant tumor suppression (∼70%) in vivo with favorable safety. This study provides a general chemical approach for ligand optimization in lysosome-targeted protein degradation, providing new ideas for the future development of peptide drugs.

PMID:
42423018
Bibliographic data and abstract were imported from PubMed on 09 Jul 2026.

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