Multivalency

14Blocking Disease Linked Lectins with Multivalent Carbohydrates

Marjon Stel and Roland J. Pieters

Department of Chemical Biology & Drug Discovery, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, PO Box 80082, 3508 TB Utrecht, the Netherlands

14.1 Introduction

Lectins are carbohydrate‐binding proteins involved in various biological phenomena of life. Since every cell surface is covered with oligosaccharide structures, a layer called the glycocalyx, lectins play an important role in signalling pathways and cell adhesion [1,2]. Carbohydrate–lectin binding often depends on multivalent interactions because the affinity of one single binding event between a lectin and a monovalent carbohydrate ligand is often quite low. However, several binding interactions together can reach high affinities [3,4]. For this reason, synthetic ligands targeting lectins benefit from multivalency, as we will see in this chapter.

Inhibiting binding of these lectins to their natural ligands can possibly prevent the diseases they are involved in. In this chapter we will discuss a selection of lectins and their inhibitors. For example, the lectins LecA and LecB from the bacterial pathogen Pseudomonas aeruginosa, the hemagglutinin protein of the influenza A virus and the cholera toxin (CT) from the bacterium Vibrio cholerae are all involved in infectious disease. Human galectins play a role in inflammation and numerous cancer mechanisms. In this chapter, we will cover a variety of ligands ...