Iterative design of a helically folded aromatic oligoamide sequence for the selective encapsulation of fructose
Iterative design of a helically folded aromatic oligoamide sequence for the selective encapsulation of fructose
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DOI：
10.1038/nchem.2195
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发表时间：
2015-04-01
期刊：
影响因子：
21.8
通讯作者：
Huc, Ivan
中科院分区：
文献类型：
--
作者：
Chandramouli, Nagula;Ferrand, Yann;Huc, Ivan
特定生物分子来宾的合成分子受体的概念设计仍然是一个难以捉摸的目标，尤其是对于诸如单糖的靶标，它们具有非常紧密的结构类似物。在这里，我们报告了一种强大的方法来产生对特定单糖具有很高选择性的受体，并且作为演示，我们开发了一种选择性地封装果糖的折叠剂。该方法使用迭代设计过程，该过程利用与分子建模和结构表征结合使用的折叠合成低聚物序列的模块化结构，以告知随后的细化。从考虑到大小，形状和氢键能力的第一原理设计开始，并利用芳香族寡酰胺的高可预测性及其结晶的倾向，在与原子尺度互补性中结合的有机溶剂中结合的序列在原子尺度上可以在原子级互补性中获得。该方案模仿了有限数量的单体单元的生物聚合物的适应性构造，为开发选择性受体提供了一般方案。
The ab initio design of synthetic molecular receptors for a specific biomolecular guest remains an elusive objective, particularly for targets such as monosaccharides, which have very close structural analogues. Here we report a powerful approach to produce receptors with very high selectivity for specific monosaccharides and, as a demonstration, we develop a foldamer that selectively encapsulates fructose. The approach uses an iterative design process that exploits the modular structure of folded synthetic oligomer sequences in conjunction with molecular modelling and structural characterization to inform subsequent refinements. Starting from a first-principles design taking size, shape and hydrogen-bonding ability into account and using the high predictability of aromatic oligoamide foldamer conformations and their propensity to crystallize, a sequence that binds to beta-D-fructopyranose in organic solvents with atomic-scale complementarity was obtained in just a few iterative modifications. This scheme, which mimics the adaptable construction of biopolymers from a limited number of monomer units, provides a general protocol for the development of selective receptors.