Development of Sequence Controlled Polymers for Antibacterial Therapeutics and Co

描述（由申请人提供）：需要新的广谱抗生素来对抗多药耐药细菌是一个日益严重的全球性问题，对人类健康构成了合理的威胁。阳离子抗菌聚合物由于其低成本、广泛的潜在用途和不容易产生耐药性的独特作用模式，代表了解决这一问题的一种有希望的方法。然而，这一领域的全面发展受到当前聚合物化学的限制。虽然小分子的现代药物化学有一系列工具来精确修饰和优化先导化合物，但控制聚合方法仍然依赖于相对较小的一组有效单体。本提案旨在通过开发一种新的序列编程大环聚合策略，系统地评估这类抗生素的结构活性关系（SAR）。通过将受控聚合方法与快速闭环/开环反应相结合，构建了结构信息

DESCRIPTION (provided by applicant): The need for new broad-spectrum antibiotics to combat multidrug resistant bacteria is a growing global problem that poses a legitimate threat to human health. Cationic antibacterial polymers represent a promising approach to address this problem due to their low cost, wide range of potential uses and a distinct mode of action that is much less prone to the development of resistance. A full development of this area, though, has been hindered by the current limitations in polymer chemistry. Whereas modern medicinal chemistry for small molecules has an arsenal of tools to precisely modify and optimize lead compounds, controlled polymerization methods are still reliant on a relatively small set of competent monomers. This proposal aims to systematically evaluate the structure activity relationships (SAR) of this class of antibiotics through the development of a novel strategy for the polymerization of sequence-programmed macrocycles. By combining a controlled polymerization method with a rapid ring closing/ring opening reaction, structural information built into the macrocycle will be translated to the polymer backbone to provide well-defined materials that have spatial control over long sequences and can incorporate chemical diversity. This strategy allows for the precise modulation of parameters that have been previously implicated in antibacterial activity: type and number of cationic groups, charge density, molecular weight and lipophilicity. The research will result in a better understanding of the structural features associated with antibacterial activity and will guide the design of next generation polymer therapeutics and coatings with improved potency and selectivity.