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Asymmetric triplex metallohelices with high and selective activity against cancer cells
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Faulkner, Alan D., Kaner, Rebecca A., Abdallah, Qasem M. A., Clarkson, Guy J., 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, Volume 6 (Number 9). pp. 797-803. doi:10.1038/nchem.2024
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Official URL: http://dx.doi.org/10.1038/nchem.2024
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: | Journal Article | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| Subjects: | R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) | ||||||||
| Divisions: | Faculty of Science > Chemistry Faculty of Science > Life Sciences (2010- ) |
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| Library of Congress Subject Headings (LCSH): | Antineoplastic agents, Simple proteins | ||||||||
| Journal or Publication Title: | Nature Chemistry | ||||||||
| Publisher: | Nature Publishing Group | ||||||||
| ISSN: | 1755-4330 | ||||||||
| Official Date: | 3 August 2014 | ||||||||
| Dates: |
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| Date of first compliant deposit: | 28 December 2015 | ||||||||
| Volume: | Volume 6 | ||||||||
| Number: | Number 9 | ||||||||
| Page Range: | pp. 797-803 | ||||||||
| DOI: | 10.1038/nchem.2024 | ||||||||
| Status: | Peer Reviewed | ||||||||
| Publication Status: | Published | ||||||||
| Access rights to Published version: | Restricted or Subscription Access | ||||||||
| Funder: | Engineering and Physical Sciences Research Council (EPSRC), University of Warwick |
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