Glycoclusters as lectin inhibitors: comparative analysis on two plant agglutinins with different folding as a step towards rules for selectivity
Murphy, Paul V.
MetadataShow full item record
This item's downloads: 39 (view details)
Andre, S,O'Sullivan, S,Gabius, HJ,Murphy, PV (2015) 'Glycoclusters as lectin inhibitors: comparative analysis on two plant agglutinins with different folding as a step towards rules for selectivity'. Tetrahedron, 71 :6867-6880.
The emerging physiological significance of carbohydrate (glycan) protein (lectin) recognition engenders the interest to design synthetic inhibitors with a high level of selectivity among natural sugar receptors. Plant agglutinins are common models to determine structure activity relationships. Focussing on the contribution of valency towards selectivity, copper-catalysed azide (sugar derivative)-alkyne (scaffold) cycloaddition yielded a panel of 10 bi- to tetravalent glycoclusters with N-acetylglucosamine as the bioactive headgroup. They were introduced into assays using (neo)glycoproteins and cell surfaces as platforms to study carbohydrate-dependent lectin binding. The ability of the bivalent compounds, which exhibit a distance profile of the sugar headgroups of about 16-21 angstrom, for intramolecular bridging of two contact sites from the eight hevein domains of wheat germ agglutinin led to comparatively high enhancements of inhibitory potency relative to a tetrameric leguminous lectin (distance profile of 50-70 angstrom between sugar-specific sites), especially for a beta-S-glycoside. The extent of inhibition at fixed concentrations of the sugar depended on the type of matrix used for the assay. Increases to tri- and tetravalency played a less important role than the anomeric position to keep cross-reactivity low, these tested topologies enabling cross-linking for both lectins. The potential for cis-interactions (intramolecular interactions), with glycoclusters serving as molecular rulers, is suggested to help designing selective blocking reagents. (C) 2015 Elsevier Ltd. All rights reserved.
This item is available under the Attribution-NonCommercial-NoDerivs 3.0 Ireland. No item may be reproduced for commercial purposes. Please refer to the publisher's URL where this is made available, or to notes contained in the item itself. Other terms may apply.
The following license files are associated with this item: