Multicolor GLUT5-permeable fluorescent probes for fructose transport analysis

Begoyan, Vagarshak; Weseliński, Łukasz J.; Xia, Shuai; Fedie, Joseph; Kannan, Srinivas; Ferrier, Alexis; Rao, Smitha; Tanasova, Marina

doi:10.1039/c7cc09809j

Cited by 26 publications

(46 citation statements)

References 27 publications

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“…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.…”

Section: Glut Specificity For Substrates and Inhibitorsmentioning

confidence: 99%

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

Holman

2020

Pflugers Arch - Eur J Physiol

141

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The SLC2 genes code for a family of GLUT proteins that are part of the major facilitator superfamily (MFS) of membrane transporters. Crystal structures have recently revealed how the unique protein fold of these proteins enables the catalysis of transport. The proteins have 12 transmembrane spans built from a replicated trimer substructure. This enables 4 trimer substructures to move relative to each other, and thereby alternately opening and closing a cleft to either the internal or the external side of the membrane. The physiological substrate for the GLUTs is usually a hexose but substrates for GLUTs can include urate, dehydro-ascorbate and myo-inositol. The GLUT proteins have varied physiological functions that are related to their principal substrates, the cell type in which the GLUTs are expressed and the extent to which the proteins are associated with subcellular compartments. Some of the GLUT proteins translocate between subcellular compartments and this facilitates the control of their function over long-and shorttime scales. The control of GLUT function is necessary for a regulated supply of metabolites (mainly glucose) to tissues. Pathophysiological abnormalities in GLUT proteins are responsible for, or associated with, clinical problems including type 2 diabetes and cancer and a range of tissue disorders, related to tissue-specific GLUT protein profiles. The availability of GLUT crystal structures has facilitated the search for inhibitors and substrates and that are specific for each GLUT and that can be used therapeutically. Recent studies are starting to unravel the drug targetable properties of each of the GLUT proteins.

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Section: Glut Specificity For Substrates and Inhibitorsmentioning

confidence: 99%

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

Holman

2020

Pflugers Arch - Eur J Physiol

141

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“…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 ].…”

Section: Looking To the Future Of Chemical Biology Approaches To Studmentioning

confidence: 99%

Chemical biology probes of mammalian GLUT structure and function

Holman

2018

Biochemical Journal

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The structure and function of glucose transporters of the mammalian GLUT family of proteins has been studied over many decades, and the proteins have fascinated numerous research groups over this time. This interest is related to the importance of the GLUTs as archetypical membrane transport facilitators, as key limiters of the supply of glucose to cell metabolism, as targets of cell insulin and exercise signalling and of regulated membrane traffic, and as potential drug targets to combat cancer and metabolic diseases such as type 2 diabetes and obesity. This review focusses on the use of chemical biology approaches and sugar analogue probes to study these important proteins.

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“…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.…”

Section: Glut5 Affinity Based On Molecular Probesmentioning

confidence: 99%

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

Elferink

Bruekers

Veeneman³

et al. 2020

Cell. Mol. Life Sci.

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The human body is able to process and transport a complex variety of carbohydrates, unlocking their nutritional value as energy source or as important building block. The endogenous glycosyl hydrolases (glycosidases) and glycosyl transporter proteins located in the enterocytes of the small intestine play a crucial role in this process and digest and/or transport nutritional sugars based on their structural features. It is for these reasons that glycosidases and glycosyl transporters are interesting therapeutic targets to combat sugar related diseases (such as diabetes) or to improve drug delivery. In this review we provide a detailed overview focused on the molecular structure of the substrates involved as a solid base to start from and to fuel research in the area of therapeutics and diagnostics.

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Multicolor GLUT5-permeable fluorescent probes for fructose transport analysis

Cited by 26 publications

References 27 publications

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

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

Chemical biology probes of mammalian GLUT structure and function

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

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