Binding of Mannose-Functionalized Dendrimers with Pea (Pisum sativum) Lectin

Abstract

Lectins are invaluable tools for chemical biology because they recognize carbohydrate arrays. Multivalent carbohydrate binding by lectins is important for processes such as bacterial and viral adhesion and cancer metastasis. A better understanding of mammalian lectin binding to carbohydrate arrays is critical for controlling these and other cellular recognition processes. Plant lectins are excellent model systems for the study of multivalent protein-carbohydrate interactions because of their robustness and ready availability. Here, we describe binding studies of mannose-functionalized poly(amidoamine) (PAMAM) dendrimers to a mitogenic lectin from Pisum sativum (pea lectin). Hemagglutination and precipitation assays were performed, and results were compared to those obtained from concanavalin A (Con A), a lectin that has been studied in more detail. Isothermal titration calorimetry (ITC) experiments are also described.

Functionalised supports with sugar dendritic ligand

“…Results previously reported by Roy et al and Cloninger et al [21][22][23][24] with glycodendrimer-lectin binding interactions strongly suggest that the structural features of these glycodendrimers offer unprecedented opportunities for the design of potent ligands for carbohydrate receptors and as models for the study of those interactions.…”

Multivalency in heterogeneous glycoenvironments: hetero-glycoclusters, -glycopolymers and -glycoassemblies

“…30 It was observed that recognition of the primary sugar by its complementary lectin was enhanced in the presence of the second sugar. Thus, the (aMan) 7 (bLact) 14 heteroglycocluster was more efficient at cross-linking Con A than the (aMan) 7 homogeneous derivative. Similarly, (aMan) 14 (bLac) 7 proved a better PNA cross-linking ligand than (bLac) 7 .…”

“…Thus, the (aMan) 7 (bLact) 14 heteroglycocluster was more efficient at cross-linking Con A than the (aMan) 7 homogeneous derivative. Similarly, (aMan) 14 (bLac) 7 proved a better PNA cross-linking ligand than (bLac) 7 . The turbidity experiments evidenced that the supplementary binding enhancement due to the secondary glycotope is sugar-specific, since the formation of the three-dimensional lattices was affected by the presence of a high concentration of the corresponding monovalent sugar in the solution.…”

“…This phenomenon, first noted by Lee and co-workers 2 and referred as the ''cluster'' or ''multivalent'' glycoside effect, 3 has found a wide range of application in biology and medicine. [4][5][6][7][8] Synthetic polyconjugates with welldefined structures have contributed to unravel the mechanisms at work, [9][10][11][12] leading eventually to useful tools for biotechnological 13,14 or therapeutic purposes. 15 Typically, these systems incorporate several copies of identical sugar motifs attached to an appropriate scaffold (molecular, dendritic, polymeric) 10,11,[16][17][18] or self-assembled in supramolecular constructs (nanoparticles, vesicles, microarrays).…”

Synthesis of PAMAM dendrimer-based fast cross-linking hydrogel for biofabrication

“…Start-burst PAMAM dendrimers are a class of synthetic polymers widely used to deliver bioactive molecules into biological systems. [20] A merit of PAMAM dendrimers is that they can be cleared through kidney [21] which is important for hydrogels used in biofabrication. Due to their water solubility, non-immunogenicity, uniform structures, and ample active functional groups for chemical modifications, they have been extensively used for cancer targeting, [22,23] drug delivery, [24,25] gene delivery, [26,27] and imaging.…”