1] University of Bordeaux, CBMN (UMR 5248), Institut Européen de Chimie et Biologie, 2 rue Escarpit, Pessac 33600, France [2] CNRS, CBMN (UMR 5248), France.
1] University of Bordeaux, IECB (UMS 3033), Institut Européen de Chimie et Biologie, 2 rue Escarpit, Pessac 33600, France [2] CNRS, IECB (UMS 3033), France [3] INSERM, IECB (US 001), France.
Nat Chem. 2015 Apr;7(4):334-41. doi: 10.1038/nchem.2195. Epub 2015 Mar 16.
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 β-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.
对于特定生物分子客体的合成分子受体的从头设计仍然是一个难以实现的目标，特别是对于单糖等结构非常相似的目标。在这里，我们报告了一种非常有效的方法来生产对特定单糖具有非常高选择性的受体，并展示了一种能够选择性包合果糖的折叠体。该方法使用迭代设计过程，利用折叠合成寡聚物序列的模块化结构，结合分子建模和结构表征，为后续的改进提供信息。从一个考虑大小、形状和氢键能力的第一性原理设计开始，并利用芳香族寡酰胺折叠体构象的高可预测性及其结晶倾向，仅经过几次迭代修饰，就得到了一个在有机溶剂中与β-D-呋喃果糖结合的序列，其原子尺度互补性。这种方案模拟了从有限数量的单体单元构建生物聚合物的适应性构建，为开发选择性受体提供了一种通用方案。
