In Vitro Selection of Cathepsin E-Activity-Enhancing Peptide Aptamers at Neutral pH

Abstract EN

The aspartic protease cathepsin E has been shown to induce apoptosis in cancer cells under physiological conditions.

Therefore, cathepsin E-activity-enhancing peptides functioning in the physiological pH range are valuable potential cancer therapeutic candidates.

Here, we have used a general in vitro selection method (evolutionary rapid panning analysis system (eRAPANSY)), based on inverse substrate-function link (SF-link) selection to successfully identify cathepsin E-activity-enhancing peptide aptamers at neutral pH.

A successive enrichment of peptide activators was attained in the course of selection.

One such peptide activated cathepsin E up to 260%, had a high affinity (KD; ∼300 nM), and had physiological activity as demonstrated by its apoptosis-inducing reaction in cancerous cells.

This method is expected to be widely applicable for the identification of protease-activity-enhancing peptide aptamers.