Development of Amphiphilic Short Peptides to Control Drug Inclusivity through Metal Complexation Reactions

Abstract

We previously reported that amphiphilic peptides containing one Lys and two His in the hydrophilic domain—KHHAAAAAA7 (KHHA7)—formed ternary complexes with intermediate metal ions and a poorly water-soluble anticancer drug—paclitaxel (Ptx)—which improved the water dispersibility of Ptx. In this study, the effect of ternary complexes of KHHA7 on cell viability is evaluated in vitro using HeLa cells. The ternary complexes reduced the cell viability by approximately 60%, suggesting that complex formation enhanced the cytotoxicity by increasing the water dispersibility of Ptx. Furthermore, the novel amphiphilic short peptides KHHAAAAAAW (KHHA6W) and KHHAAAWAAA (KHHA3WA3) were synthesized by Fmoc solid phase synthesis as dispersants for Ptx. These peptides differed from KHHA7 owing to the presence or absence of Trp and its position. The change in amino acid residues from Ala to Trp and the position of Trp in the hydrophobic domain of the amphiphilic peptide had little effect on the water dispersibility of Ptx.