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

这项提案将在伯明翰发展一个非常有前途的早期职业研究人员，博士Subhendu Karmakar，谁拥有以前的经验和技能，从顶级实验室在耶路撒冷和印度。他将获得先进的培训，在超分子和生物无机化学与生物学的接口，在领先的生物无机化学家，迈克·汉农的监督下，这将发展他的位置，他将准备好确保学术地位，推出自己的独立研究生涯在生物无机化学，支持和进一步发展欧洲的联系和合作，他将形成。除了非共价DNA结合和金属超分子和轮烷药物设计的新技术和方法，以及他将获得的可转移技能培训外，他还将向伯明翰转移他在低氧环境中激活药物的专业知识，提高伯明翰团队的能力，并使一个令人兴奋的新项目成为可能，只有通过对接他们各自的技能基础。其结果将是一种强大而创新的新方法，可以结合和干扰癌细胞复制所必需的关键DNA叉结构，并且只在癌细胞中这样做，从而最大限度地减少对正常组织的附带损伤，从而减少副作用。该项目将揭示和实现金属超分子药物设计的新视野，并改变金属治疗学的最新技术。

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.