Chemical and enzymatic synthesis of fructose analogues as probes for import studies by the hexose transporter in parasites.
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.
Azéma
L
L
Groupe de Chimie Organique Biologique, URA/CNRS ESA 5068, Université Paul Sabatier, Toulouse, France.
Bringaud
F
F
Blonski
C
C
Périé
J
J
D000818:Animals; D001692:Biological Transport; D005632:Fructose / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015335:Molecular Probes; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009132:Muscles / Q000201:enzymology; D011817:Rabbits; D014346:Trypanosoma brucei brucei / Q000378:metabolism*
D015335:Molecular Probes; D009004:Monosaccharide Transport Proteins; D005632:Fructose