Identification of a Shiga toxin A‐derived peptide internalized into Gb3 receptor‐bearing cells via interaction with the Shiga toxin B subunit

Here, we explored the potential of peptides derived from the catalytic A subunit of Shiga toxin (STxA) to be drug carriers. Using time-resolved biosensor-based assays we examined the interaction between a variety of STxA peptides (varying in length and end groups) and the cell receptor binding subunit (STxB). Peptides which bound STxB included the C-terminal α-helix protruding into the interior of STxB and the ß-strands binding to its surface. Specifically, the C-terminal 26-mer resulted in a stable complex in a physiologically relevant pH range for drug delivery. Real-time cell-binding analysis showed that the peptide-STxB complex binds to and is internalized by Gb3-overexpressing cancer cell lines with surface-exposed Gb3 receptors. It highlights STxA-derived peptides as potential as drug carriers.