Multicolor GLUT5-permeable fluorescent probes for fructose transport analysis

Abstract

The specificity of carbohydrate transporters towards their substrates poses a significant challenge for the development of molecular probes to monitor sugar uptake in cells for biochemical and biomedical applications. Herein we report a new set of coumarin-based fluorescent sugar conjugates applicable for the analysis of fructose uptake due to their free passage through the fructose-specific transporter GLUT5. The reported probes cover a broad range of the fluorescence spectrum providing essential tools for the evaluation of fructose transport capacity in live cells.

Structure, function and regulation of mammalian glucose transporters of the SLC2 family

“…Fructose transporter photolabels, based on the 2,5-anhydro-D-mannitol core structure, interact well with GLUT5 [228]. Fluorescent GLUT5 probes based on the 2,5 anhydro-mannitol ring have also recently been designed [17,126]. The presence of a hydrogen bond donor at the C-3 position of 2,5-anhydro-D-mannitol derivatives is essential for effective binding to GLUT5 and fructose transport into tumour cells.…”

Chemical biology probes of mammalian GLUT structure and function

“…We have found that photoaffinity labelling compounds (FP1 and FP2, Figure 13e,f ), which are based on 2,5-anhydro- d -mannitol, combine well with GLUT5 when this is expressed in CHO cells [ 120 ], but so far, these analogues have not been extensively tested on GLUT5-expressing tissues. Fluorescent GLUT5 probes based on the 2,5-anhydro-mannitol ring have also recently been designed [ 121 ]. The potential for targeting the unique specificity of the fructose transporters is therefore good [ 108 , 116 ]; particularly now there are good crystal structures of GLUT5 [ 61 ].…”

A comprehensive overview of substrate specificity of glycoside hydrolases and transporters in the small intestine

“…This suggest great promise for application of C-3 derived fructose conjugates in cellular uptake by GLUT5 as long as a spacer is taken with hydrogen bond donating capabilities. Finally, a new class of fluorescent probes based on C-6 coumarin substituted 2,5-AM conjugates was evaluated as application for the analysis of fructose uptake [132]. Electron withdrawing groups at the coumarin appeared to positively influence binding strength as uptake rates.…”