Multivalent Carbohydrate Recognition on a Glycodendrimer-Functionalized Flow-Through Chip

Authors

  • Hilbert M. Branderhorst,

    1. Department of Medicinal Chemistry and Chemical Biology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, P.O. Box 80082, 3508 TB Utrecht (The Netherlands), Fax: (+31) 30-2536655
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  • Rob Ruijtenbeek Dr.,

    1. Pamgene International B.V. P.O. Box 1335, 5200 BJ, 's Hertogenbosch, (The Netherlands), Fax: (+31) 73-6158081
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  • Rob M. J. Liskamp Prof. Dr.,

    1. Department of Medicinal Chemistry and Chemical Biology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, P.O. Box 80082, 3508 TB Utrecht (The Netherlands), Fax: (+31) 30-2536655
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  • Roland J. Pieters Dr.

    1. Department of Medicinal Chemistry and Chemical Biology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, P.O. Box 80082, 3508 TB Utrecht (The Netherlands), Fax: (+31) 30-2536655
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Abstract

Dendrimers were fitted out with up to eight mannose moieties by “click” chemistry. They were subsequently attached to aluminum oxide chips via a spacer that was linked to the dendrimer core; this resulted in a microarray of glycodendrimers. Binding of the glycodendrimers to the fluorescent lectins ConA and GNA was observable in real time. In a single experiment it was possible to observe the multivalency enhancement or cluster effect in the binding event. This effect was small for ConA, in agreement with its widely spaced binding sites, whereas it was large for GNA, with its twelve much more closely spaced binding sites. The dendrimer-fitted chip represents a valuable screening tool for multivalency effects. Furthermore kinetic and thermodynamic data on binding events can be deduced. Inhibition experiments are also possible with the system as was shown for ConA with α-methyl mannose as the inhibitor.

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