The Effects of Metal Ions on the Cytotoxicity and Selectivity of a Histidine-Containing Lytic Peptide

The histidine-containing peptide L5C (PAWRHAFHWAWHMLHKAA) is a histidine-rich lytic peptide. Interactions of some divalent metal ions with peptide L5C and their effects on the cell lysis activity of the peptide were studied. The presence of Cu2+ caused a secondary structure change (from random coil to alpha-helix) which resulted in the loss of cell lysis activity in peptide L5C. Binding of Zn2+ to peptide L5C also reduced the lytic activity of the peptide but Zn2+ did not affect the secondary structure of the peptides. Instead, Zn2+ induced peptide L5C aggregation. Unlike Zn2+ and Cu2+, Mg2+ had no significant effect on the activity of peptide L5C. Further experiments revealed that formed ion-peptide L5C complexes were sensitive to pH and dissociated in acidic solutions. Peptide L5C demonstrated improved pH-selectivity in the presence of trace amount of Zn2+. This property of histidine-containing lytic peptides can be used to improve their therapeutic effectiveness in the treatment of cancers.