Carbohydrates coat the surfaces of all cells and most proteins. They contain molecular information used in recognition events with carbohydrate-binding proteins (such as the lectin families) that decode this information. These bioactive carbohydrates open up a new source of novel targets for drug development.
Although carbohydrates have prominent roles in a wide range of biological processes, the currently approved drugs are mainly glycosidase inhibitors and sulphated glycosaminoglycans (that is, heparin).
Current preclinical research on lectins that are found in humans and pathogens indicates that glycomimetics could provide an alternative strategy for the treatment of inflammatory diseases (by targeting selectins) and infectious diseases (by targeting dendritic cell-specific ICAM3-grabbing non-integrin 1 (DC-SIGN), FimH, PA-I galactophilic lectin (PA-IL) and fructose-binding PA-IIL lectins).
In general, carbohydrates lack drug-like properties such as high affinity or adequate bioavailability and therapeutically relevant plasma half-lives. In addition, their large-scale production is cumbersome and expensive. When developing this class of drugs, the goal is to mimic the biological information of a functional carbohydrate with a glycomimetic that overcomes these challenges and has appropriate pharmacodynamic and pharmacokinetic properties.
Cell surface carbohydrates and carbohydrate-binding proteins mediate many key recognition events. This article reviews current progress in the development of glycomimetics and the opportunities and challenges presented by this relatively untapped source of therapeutics.
Carbohydrates are the most abundant natural products. Besides their role in metabolism and as structural building blocks, they are fundamental constituents of every cell surface, where they are involved in vital cellular recognition processes. Carbohydrates are a relatively untapped source of new drugs and therefore offer exciting new therapeutic opportunities. Advances in the functional understanding of carbohydrate–protein interactions have enabled the development of a new class of small-molecule drugs, known as glycomimetics. These compounds mimic the bioactive function of carbohydrates and address the drawbacks of carbohydrate leads, namely their low activity and insufficient drug-like properties. Here, we examine examples of approved carbohydrate-derived drugs, discuss the potential of carbohydrate-binding proteins as new drug targets (focusing on the lectin families) and consider ways to overcome the challenges of developing this unique class of novel therapeutics.