Helicates meet Rotaxanes to create promise for future disease treatment

A new approach to treating cancers and other diseases that uses a mechanically interlocked molecule as a 'magic bullet' has been designed by researchers at the University of Birmingham. Called rotaxanes, the molecules are tiny nanoscale structures that resemble a dumbbell with a ring trapped around the central post. Scientists have been experimenting with rotaxanes based on thin, thread-like central posts for a number of years, but this new design uses instead a much larger cylindrical-shaped supramolecular 'helicate' molecule - around 2nm long and 1nm wide - which have remarkable ability to bind Y-shaped junctions or forks in DNA and RNA. These forks are created when DNA replicates and, in laboratory tests, the Birmingham researchers have shown that, when they bind to the junctions, the cylinder molecules are able to stop cancer cells, bacteria and viruses from reproducing. To gain control over that binding, the team from the University's Schools of Chemistry and Biosciences, collaborated with researchers in Wuhan, in China, and Marseille, in France, to solve the challenge of identifying a ring structure large enough to fit around this central cylinder molecule. They have now shown that a giant pumpkin-shaped molecule, called a cucurbit uril) is able to host the cylinder. When the ring is present, the rotaxane molecule is unable to bind.