School of Chemistry, University of Bristol, Cantock's Close, Bristol, BS8 1TS, UK.
Nat Chem. 2012 Sep;4(9):718-23. doi: 10.1038/nchem.1409. Epub 2012 Aug 5.
Binding carbohydrates from water is a difficult task, even for the natural carbohydrate-binding proteins known as lectins. The design of synthetic lectin mimics is correspondingly challenging, especially if good selectivities are required. In previous work we showed that success is possible, but only for complex polycyclic architectures that require lengthy and low-yielding syntheses; for example, one glucose-selective system was made in 21 steps and only 0.1% overall yield. Here we report the discovery of a simple monocyclic host that matches the earlier designs, but is far more accessible as it is prepared in just five steps and 23% overall yield. The new synthetic lectin binds glucose with excellent selectivity versus other common monosaccharides (for example, ~50:1 versus galactose) and sufficient affinity for glucose sensing at the concentrations found in blood. It also features a built-in signalling system in the form of strong and guest-dependent fluorescence emission. The effectiveness and simplicity of this molecule suggests the potential for development into a new methodology for practical glucose monitoring.
从水中结合碳水化合物是一项艰巨的任务，即使是天然的碳水化合物结合蛋白（称为凝集素）也难以实现。因此，设计合成的凝集素模拟物也极具挑战性，特别是如果需要良好的选择性。在之前的工作中，我们证明了这是可行的，但仅适用于需要冗长且收率低的合成的复杂多环架构；例如，一个葡萄糖选择性系统需要 21 步合成，总收率仅为 0.1%。在这里，我们报告了一种简单的单环主体的发现，该主体与早期的设计相匹配，但由于仅需五步合成，总收率为 23%，因此更容易获得。这种新的合成凝集素对葡萄糖具有出色的选择性，与其他常见的单糖（例如，对半乳糖的选择性约为 50:1）结合，并且在血液中发现的浓度下具有足够的葡萄糖感测亲和力。它还具有内置的信号系统，表现为强烈且依赖客体的荧光发射。该分子的有效性和简单性表明，它有可能发展成为一种用于实际葡萄糖监测的新方法。
