| Summary: | The binding of polar organic molecules in water is one of the most difficult problems in molecular recognition. Carbohydrates are especially challenging targets, given their complex, hydromimetic and subtly variable structures. As a result, carbohydrate-binding proteins such as lectins often display low affinities and moderate selectivities, especially when compared to other classes of small molecule binding proteins. ‘Synthetic lectin’ mimics have been reported for several years, but have typically been still weaker, with previous approaches generally consisting of macrocycles employing aromatic surfaces bridged with amide bearing spacer units. This project aimed to investigate a new type of synthetic lectin employing bis-urea spacer units. Incorporation of this urea spacer design into anthracene tetraurea 1 afforded good affinities and selectivities, comparable to natural lectins, for cellodextrin oligosaccharide substrates (such as D-cellotriose 2). The potential of the urea spacer was fully realised when incorporated into triethylbenzene hexaurea 3 however, which shows binding affinities and selectivities for D-glucose 4 that far exceed any previous synthetic system. Receptor 3 even continues to function in complex biological media (such as human blood serum), enabling preliminary proof of concept for 3 acting as a D-glucose 4 sensor. The performance of 3 even surpasses most natural systems (such as lectins) and therefore can be considered the first true example of a synthetic biomimetic receptor for D-glucose.
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