Maximising multivalency effects in protein–carbohydrate interactions

Abstract

Multivalent carbohydrates are currently produced in many forms ranging from dendrimers, polymers, micelles, vesicles, nanoparticles to functionalized nanotubes, in order to enhance the potency of the carbohydrates as ligands or inhibitors. Variations in valency range from systems containing two carbohydrate units to those containing more than 2000. In this perspective a number of popular target proteins for multivalent binding/inhibition have been selected. The optimal systems displaying the largest multivalency effects are discussed with respect to their mechanism of multivalent binding.

A multivalent inhibitor of the DC-SIGN dependent uptake of HIV-1 and Dengue virus

“…Under these conditions, various effects can be operative. In principle, they may include 1) a high local concentration of the ligand exposed by the dendrimers (or high effective molarity, which favors statistical rebinding; [34] 2) chelation, i.e. simultaneous binding of multiple binding sites by a single dendrimer on a single DC-SIGN tetramer, or 3) the ability of the dendrimers to cluster soluble DC-SIGN tetramers.…”

A synthesis of C-glycosidic multivalent mannosides suitable for divergent functionalized conjugation

“…We sought to demonstrate this using a novel extended thiol-terminated unit with lipid-like characteristics (Scheme 1). Thus, S-alkylation of 5-bromovaleric acid with benzyl mercaptan gave the desired thioether 26 and subsequent reduction of the carboxylic acid using BH 3 .THF successfully delivered alcohol 2. 27 This material was then extended through O-alkylation with acrylonitrile to furnish novel nitrile 3.…”

“…Numerous examples of such events include host cell recognition and cancer-mediated processes [1][2][3][4][5] and many of these processes are known to involve the presentation of multivalent carbohydrate species, greatly enhancing overall ligand-receptor affinities through cooperative binding. As a result of this there is a need for robust and efficient syntheses of multivalent carbohydrate architectures as a means to provide useful tools for studying cluster-glycoside-mediated biological recognition processes.…”

Multimeric xanthates as carbonic anhydrase inhibitors

“…Especially, carbohydrate-protein interactions are notably weak at the monomer level, but can be tremendously enhanced if the ligand is displayed in a multivalent way 13 . Scientists have extensively studied the biophysical interactions among natural systems and created a plethora of artificial multivalent systems in order to understand the underlying mechanisms of multivalency [14][15][16][17][18][19][20][21][22] . The most scrutinized systems are likely lectin-carbohydrate dyads.…”