Fluorinated sugar-1-phosphates are of emerging importance as intermediates in the chemical and biocatalytic synthesis of modified oligosaccharides, as well as probes for chemical biology. Here we present a systematic study of the activity of a wide range of anomeric sugar kinases (galacto- and N-acetylhexosamine kinases) against a panel of fluorinated monosaccharides, leading to the first examples of polyfluorinated substrates accepted by this class of enzymes. We have discovered four new N-acetylhexosamine kinases with a different substrate scope, thus expanding the number of homologs available in this subclass of kinases. Lastly, we have solved the crystal structure of a galactokinase in complex with 2-deoxy-2-fluorogalactose, giving insight into changes in the active site that may account for the specificity of the enzyme toward certain substrate analogs.

氟化1-磷酸糖作为修饰寡糖的化学和生物催化合成的中间体，以及化学生物学的探针，正变得越来越重要。在这里，我们对一系列的异头糖激酶（半乳糖和N-乙酰己糖胺激酶）对一组氟化单糖的活性进行系统研究，从而导致了这类酶所接受的多氟化底物的首个实例。我们发现了四个新的N-乙酰己糖胺激酶具有不同的底物范围，因此扩大了该激酶亚类中可用的同系物的数量。最后，我们已经解决了半乳糖激酶与2-脱氧-2-氟半乳糖复合的晶体结构，从而深入了解了活性位点的变化，这可能说明了该酶对某些底物类似物的特异性。