Molecular Design of pH-Responsive Helix Peptides That Can Damage Tumor Cells Selectively.

It is known that tumor cells have a lower pH compared to normal cells. We have designed peptides that have no definite structure at neutral pH but at lower pH penetrate into the cell membrane by forming an α-helix structure and thus damage tumor cells selectively. These peptides were designed by combining a pH-responsive artificially designed α-helix structure and a flanking sequence that controls membrane insertion. In aqueous solution, some of these peptides were found to be unstructured at neutral pH and helical at acidic pH and showed destruction ability against negatively charged liposomes only at acidic pH. In living cells, one of the designed peptides induced 40% cell death against cervical cancer HeLa and breast cancer MCF-7 cells, while almost no cell death was observed against normal cells. The designed peptide can thus cause tumor cell death without side effects by responding to the peculiar environment of the cell membrane.