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

这项提议将在伯明翰培养一名前途光明的早期职业研究员Subhendu Karmakar博士，他之前在耶路撒冷和印度的顶级实验室拥有经验和技能。他将在领先的生物无机化学家Mike Hannon的指导下，在超分子和生物无机化学与生物学的界面上接受高级培训，这将使他能够获得一个学术职位，开始他自己在生物无机化学方面的独立研究生涯，并得到他将形成的欧洲联系和合作的支持和进一步发展。除了非共价dna结合、金属超分子和轮烷药物设计方面的新技术和新方法，以及他将获得的可转移技能培训，他还将把他在缺氧组织中药物激活方面的专业知识转移到伯明翰，增强伯明翰团队的能力，使一个令人兴奋的新项目成为可能，只有通过将他们各自的技能基础结合起来。结果将是一种强大而创新的新方法，可以结合并干扰癌细胞复制所必需的关键DNA叉结构，并且只在癌细胞中进行，从而最大限度地减少对正常组织的附带损害，从而减少副作用。该项目将揭示并开启金属超分子药物设计的新视野，并改变金属治疗的最新技术。

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.