Covalent Template-Directed Synthesis

由不同构建块的确定序列组成的寡聚分子代表了尚未探索的巨大化学空间。构成自然世界的纳米技术几乎完全是由这些分子，即蛋白质和核酸构建的。大自然告诉我们，序列聚合物很可能提供小分子或传统合成聚合物无法获得的广泛功能。合成序列聚合物的问题在于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确定序列的长链，并对序列空间进行进化搜索，以发现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。一个非生物学版本的体外选择实验将允许探索序列空间，以确定新的功能合成聚合物。该项目的目的是开发一种强大的新的化学方法来可靠地合成模板。生物学使用氢键将单体与模板结合，原则上，同样的策略也可以应用于合成序列聚合物。然而，在使用非共价化学用于这种模板过程中存在主要限制。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。本项目将探索一种非共价模板的替代方法，即利用不稳定的共价化学进行共价模板。

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.