Control of the cytotoxicity of dansylated polytheonamide mimic, an artificial peptide ion channel, by modification of the N-terminal structure

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• 作者：Hiroaki Itoh ; Shoko Matsutaka ; Takefumi Kuranaga ; Masayuki Inoue
• 关键词：Cytotoxic agents ; Natural products ; Structure&ndash ; activity relationships ; Peptides
• 刊名：Tetrahedron Letters
• 出版年：15 January, 2014
• 年：2014
• 卷：55
• 期：3
• 页码：728-731
• 全文大小：348 K

文摘

We demonstrate that the cytotoxicity of dansylated polytheonamide mimic (2) is controlled by chemical modification of its N-terminal structure. Dansylated polytheonamide mimic (2) is an ion channel peptide which displays potent cytotoxicity against P388 mouse leukemia cells (IC₅₀ = 12 nM). To modulate its cytotoxicity, three analogues of 2, possessing distinct N-terminal structures with different hydrophobicities, were synthesized and their cytotoxicities were evaluated. This focused structure-activity relationship study unveiled that the cytotoxicity of 2 is enhanced 10-fold by simply changing its N-terminal 5,5-dimethyl-2-oxohexanamide to the more hydrophobic palmitamide. The data obtained here provide new understanding for the functional control of the artificial ion channel peptide 2.