Faulkner, Alan D., Kaner, Rebecca A., Abdallah, Qasem M. A., Clarkson, Guy, Fox, David J., Gurnani, Pratik, Howson, Suzanne E., Phillips, Roger M., Roper, David I., Simpson, Daniel H. and Scott, Peter (2014) Asymmetric triplex metallohelices with high and selective activity against cancer cells. Nature Chemistry, 6 (9). pp. 797-803. ISSN 17554330
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Abstract
Small cationic amphiphilic α-helical peptides are emerging as agents for the treatment of cancer and infection, but they are costly and display unfavourable pharmacokinetics. Helical coordination complexes may offer a three-dimensional scaffold for the synthesis of mimetic architectures. However, the high symmetry and modest functionality of current systems offer little scope to tailor the structure to interact with specific biomolecular targets, or to create libraries for phenotypic screens. Here, we report the highly stereoselective asymmetric self-assembly of very stable, functionalized metallohelices. Their anti-parallel head-to-head-to-tail ‘triplex’ strand arrangement creates an amphipathic functional topology akin to that of the active sub-units of, for example, host-defence peptides and p53. The metallohelices display high, structure-dependent toxicity to the human colon carcinoma cell-line HCT116 p53++, causing dramatic changes in the cell cycle without DNA damage. They have lower toxicity to human breast adenocarcinoma cells (MDA-MB-468) and, most remarkably, they show no significant toxicity to the bacteria methicillin-resistant Staphylococcus aureus and Escherichia coli.
At a glance
Item Type: | Article |
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Subjects: | R Medicine > R Medicine (General) R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) |
Schools: | School of Applied Sciences |
Related URLs: | |
Depositing User: | Sara Taylor |
Date Deposited: | 19 May 2015 14:08 |
Last Modified: | 28 Aug 2021 18:09 |
URI: | http://eprints.hud.ac.uk/id/eprint/24604 |
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