Multivalent saccharides: development of new approaches for inhibiting the effects of glycosphingolipid-binding pathogens

A number of diseases are initiated by the adherence of viruses, bacteria, or bacterial toxins to cell surface carbohydrates, a number of which are components of glycosphingolipids (GSLs). Studies of the binding of lectins indicated that many adhered weakly to monomeric carbohydrate ligands. The seminal observation that lectins adhered more strongly to a ligand with multiple carbohydrate binding sites initiated a plethora of studies designed to identify effective "multivalent" carbohydrate ligands for pathogens expressing multiple carbohydrate-binding sites. In addition to more completely defining ligand specificity of the carbohydrate-binding pathogen, identification of "multivalent" carbohydrate ligands has led to studies of their efficacy as pathogen inhibitors. This commentary focuses on pathogens that recognize the carbohydrate portion of GSLs. Because many GSL-binding pathogens have been shown to bind "multivalent" saccharides, approaches for identifying and preparing them as well as methods for characterizing their effectiveness as ligands are reviewed. Also discussed are areas of promise that should be investigated and pitfalls that might be encountered in the development of "multivalent" saccharides as pharmacologic agents. (C) 2002 Elsevier Science Inc. All rights reserved.