title: Synthesis and evaluation of fructose analogues as inhibitors of the D-fructose transporter GLUT5.
abstract: 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.
authors.affiliation: Department of Biology and Biochemistry, University of Bath, UK.
authors.forename: A
authors.initials: A
authors.lastname: Tatibouët
authors.forename: J
authors.initials: J
authors.lastname: Yang
authors.forename: C
authors.initials: C
authors.lastname: Morin
authors.forename: G D
authors.initials: GD
authors.lastname: Holman
mesh_terms: 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
chemical_list: D002250:Carbon Radioisotopes; D051296:Glucose Transporter Type 5; D009004:Monosaccharide Transport Proteins; D005632:Fructose