Investigating the Potential Of Polymer-Scaffolded Dynamic Combinatorial Libraries

研究聚合物支架动态组合文库的潜力

• 批准号: EP/G066507/1
• 负责人: David Fulton
• 金额: $ 40.56万
• 依托单位: Newcastle University
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2009
• 资助国家: 英国
• 起止时间: 2009 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FG066507%2F1
• 关键词: Investigating; Potential; Polymer; Scaffolded; Dynamic

We propose to develop a new, simple and low-cost method to create wholly synthetic macromolecules which can selectively recognise and bind to target molecules, or catalyse chemical reactions of interest. These macromolecules can be considered as synthetic mimics of proteins, a class of macromolecule found in all living systems which over billions of years have perfected their molecular recognition and catalytic abilities. The proposed approach to developing synthetic protein mimics involves the application of concepts from the emerging field of dynamic combinatorial chemistry, in which building blocks are self-assembled around a template molecule. The special nature of this 'molding' process provides a mechanism for optimising the interactions between the template and receptor, a significant advance over existing methods for designing receptors. The development of an effective method to create 'designer' macromolecules will be of considerable benefit in numerous applications where protein-based technologies are already important. Clinical in vitro diagnostics, for instance, are heavily reliant on sophisticated macromolecular receptors which are often expensive and difficult to produce. Our approach could allow the rapid creation of low-cost synthetic alternatives. Furthermore, our method may be useful in creating new macromolecular catalysts for reactions in which natural or engineered proteins are not efficient or simply not available. Such technology would be immensely important to the pharmaceutical and fine chemicals industries.

我们建议开发一种新的，简单的和低成本的方法来创建完全合成的大分子，可以选择性地识别和结合到目标分子，或催化感兴趣的化学反应。这些大分子可以被认为是蛋白质的合成模拟物，蛋白质是在所有生命系统中发现的一类大分子，经过数十亿年的发展，它们已经完善了分子识别和催化能力。所提出的开发合成蛋白质模拟物的方法涉及应用动态组合化学新兴领域的概念，其中构建模块围绕模板分子自组装。这种“成型”过程的特殊性质提供了一种优化模板和受体之间相互作用的机制，这是对现有受体设计方法的重大进步。开发一种有效的方法来创建“设计师”大分子将在许多应用中具有相当大的好处，其中基于蛋白质的技术已经很重要。例如，临床体外诊断严重依赖复杂的大分子受体，这些受体通常昂贵且难以生产。我们的方法可以快速创建低成本的合成替代品。此外，我们的方法可能有助于创造新的大分子催化剂，用于天然或工程蛋白质无效或根本不可用的反应。这种技术对制药和精细化学品工业非常重要。

项目成果

Molecular Recognition-Mediated Transformation of Single-Chain Polymer Nanoparticles into Crosslinked Polymer Films.

• DOI: 10.1002/anie.201706379
• 发表时间: 2017-10-09
• 期刊: Angewandte Chemie (International ed. in English)
• 作者: Mahon CS;McGurk CJ;Watson SMD;Fascione MA;Sakonsinsiri C;Turnbull WB;Fulton DA
• 通讯作者: Fulton DA

Molecular Recognition-Mediated Transformation of Single-Chain Polymer Nanoparticles into Crosslinked Polymer Films

分子识别介导的单链聚合物纳米颗粒向交联聚合物薄膜的转化

• DOI: 10.1002/ange.201706379
• 发表时间: 2017
• 期刊: Angewandte Chemie
• 作者: Mahon C

Templation-induced re-equilibration in polymer-scaffolded dynamic combinatorial libraries leads to enhancements in binding affinities

• DOI: 10.1039/c3sc51413g
• 发表时间: 2013-07
• 期刊: Chemical Science
• 影响因子: 8.4
• 作者: Clare S. Mahon;D. Fulton