Chemical and enzymatic synthesis of fructose analogues as probes for import studies by the hexose transporter in parasites Original Research Article

Various d-fructose analogues modified at C-1 or C-6 positions were synthesized from d-glucose by taking advantage of the Amadori rearrangement or using the aldol condensation between dihydroxyacetone phosphate and appropriate aldehyde catalyzed by fructose 1,6-diphosphate aldolase from rabbit muscle. The affinities of the analogues for the glucose transporter expressed in the mammalian form of Trypanosoma brucei were determined by inhibition of radiolabelled 2-deoxy-d-glucose (2-DOG) transport using zero-trans kinetic analysis. Interestingly, the analogues bearing an aromatic group (i.e. a fluorescence marker) at C-1 or C-6 positions present comparable apparent affinities to d-fructose for the transporter. This result could find applications for hexose transport studies and also provides criteria for the design of glucose import inhibitors.