Synthesis and cytotoxic activity of new peptides containing basic amino acid residues

In search of more potent compounds endowed with a cytotoxic activity, a new series of basic peptides was synthesized using solid-phase methods. All peptides were purified by preparative reverse-phase HPLC and characterized by electrospray mass spectrometry. The cytotoxic activity was determined in cultured HeLa cells. The hexadecapeptides 5 and 6 showed a 50% inhibition at the concentration of 30 μg/ml. The salmina and the polyamino acids of L-arginine, L-histidine and L-lysine, containing sixteen residues, were virtually inactive. This demonstrates that a specific peptide sequence is necessary to obtain a positive response in HeLa test. polypeptides, such as protamines, to display the inhibitory activity in HeLa test. Lastly, to verify if the cytotoxicity of our active hexadecapeptides is due to sequence specificity, we have prepared three polymers of L-arginine, L-histidine and L-lysine, each containing sixteen residues. The cytotoxic activity of all compounds was assessed using cultured HeLa cells.