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-fructo-furanose. Therefore, the C-6 position offers the most suitable position for development of affinity probes and labels for exploring GLUT5 biochemistry. (C) 2000 Elsevier Science Ltd. All rights reserved.