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A new approach to treating cancers and other diseases that uses a mechanically interlocked molecule like a “magic bullet” was designed by researchers at the University of Birmingham.
Called rotassanes, the molecules are tiny nanoscale structures that resemble a dumbbell with a ring trapped around the central pole. Scientists have been experimenting with rotaxanes based on thin, thread-like center pins for a number of years, but this new design instead uses a much larger cylindrical-shaped supramolecular molecule – about 2 nm long and 1 nm wide – which has remarkable ability to bind Y-shaped junctions or forks in DNA and RNA.
These forks are created when DNA replicates and, in laboratory tests, Birmingham researchers have shown that when they bind to the junctions, the cylinder molecules are able to stop the reproduction of cancerous cells, bacteria and viruses.
To gain control over that link, the University’s Schools of Chemistry and Biosciences team collaborated with researchers in Wuhan, China, and Marseille, France, to solve the challenge of identifying a ring structure large enough to fit. to this central cylinder molecule. They have now shown that a giant pumpkin-shaped molecule, called a cucurbit, is capable of housing the cylinder. When the ring is present, the rotaxane molecule is unable to bind.
To prevent the cylinder from sliding out of the pumpkin-shaped ring, the researchers added branches to each end of the cylinder. They showed that the cylinder is then mechanically locked inside the ring and that they can use it to control how the supramolecular cylinder interacts with RNA and DNA.
The results, published in Journal of the American Chemical Society, show not only how these complex molecules can be produced simply and efficiently, but also how the number of branches can be used to regulate how quickly the cylinder can exit the pumpkin-shaped ring – from quick to not at all. . This allows the temporal control of the recognition of the fork and therefore of the biological activity.
Lead researcher Professor Mike Hannon explains: ‘This is a very promising new approach that harnesses solid, proven chemistry in a whole new way that has the potential for targeted treatment of cancers and other diseases.
“Our approach is very different from major anticancer drugs that commonly target all cells in the body, not just cancer cells. The rotaxane molecule holds the promise that by turning it on and off as required, it can specifically target and inhibit cancer cells with a high degree of accuracy. “
The University of Birmingham Enterprise has filed a patent application covering the structure and design of these new rotassans, and the team has already begun work to explore a variety of applications for this approach.
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