Peptide Nanostructure Kills Cancer Cells

By adding crown ether moieties to a polypeptide, chemists in Canada have created a nanoscale chemotherapeutic compound that can selectively and efficiently kill prostate cancer cells (Chem. Commun., DOI: 10.1039/b800528a). The compound, designed by chemistry professor Normand Voyer and graduate students Pierre-Luc Boudreault, Mathieu Arseneault, and François Otis of Laval University, is based on a 14-residue helical peptide that contains four crown ethers (shown). Voyer's group previously showed that this 14-mer possesses a powerful ability to disrupt cell membranes. To make the compound selective for prostate cancer cells, the chemists added two γ-linked glutamate residues to the compound's N-terminus. These residues decrease the hydrophobicity of the molecule and render it inactive until it reaches the surface of the prostate cancer cell. There, an enzyme that's specifically expressed on the surface of prostate cancer cells cleaves off the γ-linked glutamates, releasing the membrane-puncturing compound. Voyer believes that the compound's size of approximately 2 nm is an important factor in its lysing activity. He says the peptide nanostructure constitutes an important early "step toward efficient nanochemotherapeutics exploiting the unusual bioactivity of synthetic membrane-active compounds of nanometer dimensions."