Covalent Template-Directed Synthesis

由不同构件的确定序列组成的低聚分子代表了一片尚未探索的巨大化学空间。构成自然界的纳米技术几乎完全由这样的分子构成，即蛋白质和核酸。大自然告诉我们，序列聚合物很可能提供获得小分子或传统合成聚合物无法获得的广泛功能的途径。合成序列聚合物的问题是我们没有有用的工具来制造它们。生物学使用核酸模板来合成已定义序列的长链，并对序列空间进行进化搜索，以找出哪些序列具有有趣的特性。因此，高效模板合成方案的开发将为合成序列聚合物的开发开辟道路。体外选择实验的非生物版本将允许探索序列空间，以鉴定新的功能性合成聚合物。这个项目的目的是开发一种强大的新的化学方法来合成可靠的模板。生物学使用氢键将单体结合到模板上，原则上，同样的策略可以应用于合成序列聚合物。然而，将非共价化学用于这种模板过程有很大的局限性。如果我们要找到一种可靠的化学方法来合成模板，就需要一种不同的方法。这个项目将探索一种替代非共价模板的方法，即使用不稳定的共价化学的共价模板。

Oligomeric molecules composed of defined sequences of different building blocks represent a huge area of as yet unexplored chemical space. The nanotechnology that constitutes the natural world is built almost entirely from such molecules, i.e. proteins and nucleic acids. Nature teaches us that sequence polymers are likely to provide access to a wide range of functionality that is not accessible with small molecules or conventional synthetic polymers. The problem with synthetic sequence polymers is that we do not have useful tools to make them. Biology uses nucleic acid templates both for synthesis of long chains of defined sequence, and for evolutionary searching of sequence space to find which sequences have interesting properties. Thus the development of efficient template synthesis protocols would open the way to exploitation of synthetic sequence polymers. An abiological version of the in vitro selection experiment would allow exploration of sequence space to identify new functional synthetic polymers. The aim of this project is to develop a powerful new chemical approach for reliable template synthesis. Biology uses hydrogen-bonds to bind monomers to a template, and in principle, the same strategy could by applied to synthetic sequence polymers. However, there are major limitations in using non-covalent chemistry for such templating processes. If we are to find a reliable chemical method for template synthesis, a different approach will be required. This project will explore an alternative to non-covalent templating, covalent templating using labile covalent chemistry.