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 α-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.

含组氨酸的肽L5C（PAWRHAFHWAWHMLHKAA）是一种富含组氨酸的裂解肽。研究了一些二价金属离子与肽L5C的相互作用以及它们对该肽细胞裂解活性的影响。Cu²⁺的存在导致二级结构改变（从无规卷曲变为α - 螺旋），从而使肽L5C的细胞裂解活性丧失。Zn²⁺与肽L5C的结合也降低了该肽的裂解活性，但Zn²⁺不影响肽的二级结构。相反，Zn²⁺诱导肽L5C聚集。与Zn²⁺和Cu²⁺不同，Mg²⁺对肽L5C的活性没有显著影响。进一步的实验表明，形成的离子 - 肽L5C复合物对pH敏感，并在酸性溶液中解离。在微量Zn²⁺存在的情况下，肽L5C表现出更好的pH选择性。含组氨酸裂解肽的这一特性可用于提高其在癌症治疗中的治疗效果。