Publications [#234245] of Eric J. Toone

Journal Articles

1. Corbell, JB; Lundquist, JJ; Toone, EJ, Biological and Calorimetric Analysis of Multivalent Glycodendrimers Ligands for Concanavalin A., Tetrahedron Asymm., vol. 11 no. 1 (2000), pp. 95-111 [doi]
   (last updated on 2026/01/13)

   Abstract:
   The cluster glycoside effect - the observation that multivalent glycosides bind to their polyvalent protein receptors with apparent affinities greater than those that can be rationalized solely on the basis of valency - is by now a well established phenomenon. As part of a continuing effort to provide a molecular basis for the cluster glycoside effect, we report here the synthesis of two series of mannosylated dendritic ligands and their performance in a range of competitive and non-competitive binding assays, including hemeagglutination inhibition (HIA), enzyme-linked lectin assays (ELLA) and isothermal titration microcalorimetry (ITC). The first series of ligands contained a semi-rigid glycylglycine spacer and showed no significant performance enhancement in any binding studies. The second series of ligands contained a flexible tetraethylene glycol spacer; these ligands showed marked enhancements at tetravalent and hexavalent levels in both HIA (IC50=3 and<0.8 μM, respectively) and ITC (K(A)=6.2x104 and 1.5x106 M-1, respectively) studies. In all cases, the thermodynamic parameters of association are consistent with non-specific aggregation rather than enhanced lectin-ligand affinity. This conclusion is reinforced by the lack of enhancements in ligand activity observed in ELLA studies. Copyright (C) 2000 Elsevier Science Ltd.