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Issue 23, 2015
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New fluorinated fructose analogs as selective probes of the hexose transporter protein GLUT5

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Abstract

Facilitated hexose transporters (GLUTs) mediate the transport of hexoses and other substrates across the membranes of numerous cell types, and while some are expressed ubiquitously (e.g., GLUT1), others are more tissue specific (e.g., GLUT5). These properties have been exploited for the imaging of cancer cells by the use of hexose based probes, including fluorinated hexose derivatives for use with positron emission tomography (PET). However, design of new probes has been hampered by a limited understanding of how GLUT transporters interact with their substrates at the molecular level. Two fluorinated fructose surrogates designed for uptake by the GLUT5 transporter are described here: 3-deoxy-3-fluoro-D-fructose (3-FDF) and 1-deoxy-1-fluoro-2,5-anhydromannitol (1-FDAM). Synthesis (both cold and radiolabeled) and in vitro analysis of their transport characteristics in two breast cancer cell lines (EMT-6 and MCF-7) expressing GLUT5 are detailed. Both analogues are readily taken up into both cancer cell lines, with uptake mediated primarily by GLUT5. They also have low IC50 values, indicating a high affinity for the transporter, suggesting that the uptake of these probes would be unaffected by endogenously circulating fructose. Selective uptake by GLUT5 was also demonstrated in Xenopus oocytes. Finally, these results are the first demonstration that a hexose existing predominantly in the pyranose ring structure (3-FDF) is transported by GLUT5, strongly suggesting that this transporter can handle both furanose and pyranose forms of fructose.

Graphical abstract: New fluorinated fructose analogs as selective probes of the hexose transporter protein GLUT5

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Publication details

The article was received on 13 Feb 2015, accepted on 11 May 2015 and first published on 11 May 2015


Article type: Paper
DOI: 10.1039/C5OB00314H
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Org. Biomol. Chem., 2015,13, 6511-6521

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    New fluorinated fructose analogs as selective probes of the hexose transporter protein GLUT5

    O. Soueidan, B. J. Trayner, T. N. Grant, J. R. Henderson, F. Wuest, F. G. West and C. I. Cheeseman, Org. Biomol. Chem., 2015, 13, 6511
    DOI: 10.1039/C5OB00314H

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