DNA-programmed bispecific peptide assemblies for delivering cytotoxic payload to cells expressing EGFR and MET receptors.

ABSTRACT: Bispecific agents capable of simultaneously targeting two distinct cell surface receptors promise enhanced specificity and efficacy in cancer therapy. Here, we report a strategy for the rapid optimization of compact bispecific agents using nucleic acid hybridization to display peptide ligands for both the epidermal growth factor receptor (EGFR) and the mesenchymal-epithelial transition factor (MET). The self-assembly process involved 20 and 21 nucleotide (nt) long DNA-peptide conjugates and 41-46 nt template strands, which precisely controlled the spatial arrangement of the EGFR-targeting peptide GE11 and the MET-binding bicyclic peptide GE137. We introduce improved synthetic methods for the challenging construction and functionalization of GE137, enabling its efficient conjugation to olig

SUBMITTER: Ghosh P 

PROVIDER: S-EPMC12694606 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature