Mimicking nature with synthetic macromolecules capable of recognition
Mimicking nature with synthetic macromolecules capable of recognition
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DOI：
10.1038/nchem.1994
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发表时间：
2014-08-01
期刊：
影响因子：
21.8
通讯作者：
Fulton, David A.
中科院分区：
文献类型：
--
作者：
Mahon, Clare S.;Fulton, David A.
自然界经过数十亿年的进化，组装了大量能够精细识别分子的聚合物大分子。这一功能源于对它们的生物合成施加的精确控制，导致关键残基被固定在适当的位置以与目标底物相互作用。对于化学家来说，开发能够模仿这种行为的完全合成的大分子类似物是一个相当大的挑战，因为他们缺乏自然界中用来以如此精确的方式组装聚合物的“生物机械”。在应对这一挑战的过程中，熟悉的化学概念，如组合方法和超分子相互作用，已被应用于大分子领域。从有限的残基出发，合成的大分子已经显示出与目标蛋白惊人的高结合亲和力，甚至在体内具有有用的活性。当人们考虑到这些合成大分子受体内在的异质性时，这些观察结果就更加令人惊讶，并引发了关于我们对受体设计的假设的有趣的问题。
Nature has, through billions of years of evolution, assembled a multitude of polymeric macromolecules capable of exquisite molecular recognition. This functionality arises from the precise control exerted over their biosynthesis that results in key residues being anchored in the appropriate positions to interact with target substrates. Developing 'wholly synthetic' macromolecular analogues that can mimic this behaviour presents a considerable challenge to chemists, who lack the 'biological machinery' used in nature to assemble polymers with such precision. In addressing this challenge, familiar chemical concepts, such as combinatorial methods and supramolecular interactions, have been adapted for application in the macromolecular arena. Working from a limited set of residues, synthetic macromolecules have been produced that display surprisingly high binding affinities towards target proteins, even possessing useful in vivo activities. These observations are all the more surprising when one considers the heterogeneity inherent within these synthetic macromolecular receptors, and provoke intriguing questions regarding our assumptions about the design of receptors.