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 t he fructose transporter GLUT5. Interaction with a series of fructofuranosid es and fructopyranosides suggests that both furanose and pyranose ring form s of D-fructose combine with GLUT5. The epimers of D-fructose all have low affinity for GLUT5 suggesting that the transporter requires all hydroxyls t o be in the fructo-configuration. Similarly there is poor tolerance of all allyl derivatives of D-fructose except 6-O-allyl-D-fructo-furanose. Therefo re, the C-6 position offers the most suitable position for development of a ffinity probes and labels for exploring GLUT5 biochemistry. (C) 2000 Elsevi er Science Ltd. All rights reserved.