Synthesis and evaluation of fructose analogues as inhibitors of the D-fructose transporter GLUT5.
We have examined the specificity and binding-site spatial requirements of the fructose transporter GLUT5. Interaction with a series of fructofuranosides and fructopyranosides suggests that both furanose and pyranose ring forms of D-fructose combine with GLUT5. The epimers of D-fructose all have low affinity for GLUT5 suggesting that the transporter requires all hydroxyls to be in the fructo-configuration. Similarly there is poor tolerance of all allyl derivatives of D-fructose except 6-O-allyl-D-fructofuranose. Therefore, the C-6 position offers the most suitable position for development of affinity probes and labels for exploring GLUT5 biochemistry.
Tatibouët
A
A
Department of Biology and Biochemistry, University of Bath, UK.
Yang
J
J
Morin
C
C
Holman
G D
GD
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D016466:CHO Cells; D002250:Carbon Radioisotopes; D006224:Cricetinae; D005632:Fructose / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D051296:Glucose Transporter Type 5; D007700:Kinetics; D015394:Molecular Structure; D009004:Monosaccharide Transport Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
D002250:Carbon Radioisotopes; D051296:Glucose Transporter Type 5; D009004:Monosaccharide Transport Proteins; D005632:Fructose