Glycomimetic drugs--a new source of therapeutic opportunities

Abstract

Carbohydrates are ubiquitous and represent the most abundant class of molecules in nature. All cell surfaces are coated with complex carbohydrates where they act as recognition molecules for other cells, functional molecules, and pathogens. Consequently, they are involved in disease indications as diverse as inflammation, cancer, and infectious disease. In general, native carbohydrates lack the properties necessary for efficacious drugs and historically have not been successful candidates to capitalize on these applications. Understanding the bioactive conformation and molecular interactions of functional carbohydrates, however, allows the rational design of small molecule glycomimetics that exhibit improved drug-like properties such as increased affinity, serum half-life, stability, and bioavailability. Recent advances in analytical techniques (i.e., NMR, x-ray crystallization), molecular modeling, and synthetic organic chemistry allow the design of potent glycomimetic compounds, which opens the door to a new class of therapeutic drugs to target molecular mechanisms that can address many of the current unmet needs in the treatment of disease.