Tumour Selective Activation of Rotaxanated DNA-fork-binding Metallo-supramolecular Nano-cylinder Helicates

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This proposal will develop at Birmingham a highly promising early career researcher, Dr Subhendu Karmakar, who has previous experience and skills from top labs in Jerusalem and India. He will gain advanced training at the interface of supramolecular and bioinorganic chemistry with biology, under the supervision of a leading bioinorganic chemist, Mike Hannon, that will develop him to a position where he will be ready to secure an academic position to launch his own independent research career in Bioinorganic Chemistry, supported by and further developing the European links and collaborations he will have formed. Alongside the new techniques and approaches in non-covalent DNA-binding and metallo-supramolecular and rotaxane drug designs, and the transferable skills training he will gain, he will transfer to Birmingham his expertise in activation of drugs in hypoxic tisues, enhancing the capabilities of the Birmingham team and enabling an exciting new project made possible only by interfacing their respective skill bases. The result will be a powerful and innovative new approach to agents that will bind and interfere with critical DNA fork structures essential to cancer cell replication and which will do so only in cancer cells and so minimise collateral damage to normal tissue and thus side-effects. The project will reveal and enable new horizons for metallo-supramolecular drug design and transform the state-of-the-art for metallo-therapeutics.