کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5271112 | 1385432 | 2014 | 4 صفحه PDF | دانلود رایگان |

- Polytheonamide B is an ion channel forming peptide that displays potent cytotoxicity.
- Dansylated polytheonamide mimic was designed as its simplified analogue.
- The three analogues of the mimic were synthesized and biologically evaluated.
- A 10-fold enhancement in the cytotoxicity was attained by increasing the log P value.
- The data provide new understanding for the functional control of the ion channel.
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 (IC50Â =Â 12Â 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.
Journal: Tetrahedron Letters - Volume 55, Issue 3, 15 January 2014, Pages 728-731