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Issue 15, 2011
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Symmetric dithiodigalactoside: strategic combination of binding studies and detection of selectivity between a plant toxin and human lectins

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Abstract

Thioglycosides offer the advantage over O-glycosides to be resistant to hydrolysis. Based on initial evidence of this recognition ability for glycosyldisulfides by screening dynamic combinatorial libraries, we have now systematically studied dithiodigalactoside on a plant toxin (Viscum album agglutinin) and five human lectins (adhesion/growth-regulatory galectins with medical relevance e.g. in tumor progression and spread). Inhibition assays with surface-presented neoglycoprotein and in solution monitored by saturation transfer difference NMR spectroscopy, flanked by epitope mapping, as well as isothermal titration calorimetry revealed binding properties to VAA (Ka: 1560 ± 20 M−1). They were reflected by the structural model and the affinity on the level of toxin-exposed cells. In comparison, galectins were considerably less reactive, with intrafamily grading down to very minor reactivity for tandem-repeat-type galectins, as quantitated by radioassays for both domains of galectin-4. Model building indicated contact formation to be restricted to only one galactose moiety, in contrast to thiodigalactoside. The tested glycosyldisulfide exhibits selectivity between the plant toxin and the tested human lectins, and also between these proteins. Therefore, glycosyldisulfides have potential as chemical platform for inhibitor design.

Graphical abstract: Symmetric dithiodigalactoside: strategic combination of binding studies and detection of selectivity between a plant toxin and human lectins

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Publication details

The article was received on 22 Dec 2010, accepted on 21 Apr 2011 and first published on 21 Apr 2011


Article type: Paper
DOI: 10.1039/C0OB01235A
Citation: Org. Biomol. Chem., 2011,9, 5445-5455
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    Symmetric dithiodigalactoside: strategic combination of binding studies and detection of selectivity between a plant toxin and human lectins

    S. Martín-Santamaría, S. André, E. Buzamet, R. Caraballo, G. Fernández-Cureses, M. Morando, J. P. Ribeiro, K. Ramírez-Gualito, B. de Pascual-Teresa, F. J. Cañada, M. Menéndez, O. Ramström, J. Jiménez-Barbero, D. Solís and H. Gabius, Org. Biomol. Chem., 2011, 9, 5445
    DOI: 10.1039/C0OB01235A

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