Probing Bacterial-Toxin Inhibition with Synthetic Glycopolymers Prepared by Tandem Post-Polymerization Modifications Role of Linker Length and Carbohydrate Density

摘要

Protein-carbohydrate interactions mediate many critical biological recognition processes, such as those involved in cell signaling, fertilization, and inflammation, as well as the adhesion of viruses and bacterial toxins. The proteins responsible for deciphering this information are termed lectins, which specifically (and noncovalently) bind carbohydrates based on their branching pattern, stereochemistry, and chemical functionality. The protein-saccharide interactions are usually weak, but are amplified by clustered saccharides, resulting in a binding constant which is greater than the simple sum of the total number of ligands. This observation is referred to as the "cluster glycoside" effect. Considering this information, glycopolymers are attractive materials to interact with lectins and have been shown to display binding affinities several orders of magnitude greater than a single carbohydrate molecule. One of the most attractive applications of glycopolymers is to interfere with the binding of lectins from a pathogen to the host organism and therefore prevent infection from occurring; this is known as anti-adhesion therapy.