Clinical applications of the naturally occurring or synthetic glycosylated low molecular weight drugs

Four major types of biomacromolecules are nucleic acids (DNAs and RNAs), proteins, lipids, and glycans. Only carbohydrates or glycans are a universal existence in all types of the biomacromolecules. The monosaccharides deoxyribose and ribose are an integral part of DNA and RNA structures. Glycosylated proteins and glycosylated lipids are common in all life forms. As expected, many well-known glycosylated low molecular weight drugs (GLMWDs) that target biomacromolecules, such as antibiotics, anticancer, steroids, and antidiabetic therapeutics, are naturally made glycosylated products. A drug usually consists of pharmacophoric components that are responsible for molecular target binding, an inert nonbinding component that acts as a scaffold, and the auxiliary part that contributes to the acceptable pharmacodynamics and pharmacokinetic properties of the drug. Glycans themselves can serve as pharmocophores. Moreover, the rigid molecular ring systems in the glycan can serve as molecular templates to display other pharmacophores in well-defined spatial orientations. Furthermore, glycosylated drugs usually have better solubility and permeability to allow sufficient amount of the drugs to move around. In the field of pharmacology, low molecular weight drugs refer to the drugs with the molecular weight less than 900 Da and most of modern medicines are small molecule based. This review covers eight major types of GLMWD, including aminoglycosides, cardiac glycosides, macrolides, steroids, nucleosides, thioglycosides, glycopeptides, and alditols. Their glycosylated structures, pharmacological effects, clinical applications, and adverse effects will be presented and discussed. Our goal is to provide the comprehensive information and references for GLMWDs to promote their research and development in future.