期刊
ACS APPLIED BIO MATERIALS
卷 4, 期 3, 页码 2442-2452出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsabm.0c01407
关键词
peptide design; helix; structure formation; pH response; cytotoxicity; anticancer drug
资金
- MEXT of Japan
- Cooperative Research Program of Network Joint Research Center for Materials and Devices
Researchers have designed peptides that can penetrate cell membranes and selectively destroy tumor cells in low pH environments. These peptides were found to induce tumor cell death effectively while showing minimal effects on normal cells in experiments.
It is known that tumor cells have a lower pH compared to normal cells. We have designed peptides that have no definite structure at neutral pH but at lower pH penetrate into the cell membrane by forming an alpha-helix structure and thus damage tumor cells selectively. These peptides were designed by combining a pH-responsive artificially designed alpha-helix structure and a flanking sequence that controls membrane insertion. In aqueous solution, some of these peptides were found to be unstructured at neutral pH and helical at acidic pH and showed destruction ability against negatively charged liposomes only at acidic pH. In living cells, one of the designed peptides induced 40% cell death against cervical cancer HeLa and breast cancer MCF-7 cells, while almost no cell death was observed against normal cells. The designed peptide can thus cause tumor cell death without side effects by responding to the peculiar environment of the cell membrane.
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