Abstract
Many of the glycans exist as glycoconjugates such as glycoproteins, glycolipids, and glycosaminoglycans, which have a variety of functions based on the vast structural diversity. The cell surface glycoconjugates form a glycocalyx to cover and protect the cell from the environments. Consequently, cell surface glycans play important roles in the various recognition events. Glycans are involved in various life phenomena such as immunity, infection, inflammation, cancer, aging and etc. Aberrant glycosylation is linked to various diseases such as type 2 diabetes, emphysema, neurodegenerative diseases, cancer, and etc. The pathogenesis of glycan-related diseases such as congenital disorders of glycosylation (CDGs), lysosomal diseases, some forms of congenital muscular dystrophy has been clarified. Diagnostic agents based on aberrant glycosylation on cell surface and glycoproteins in cancer have been developed as cancer biomarkers (e.g., pancreatic, ovarian, liver, and prostate cancers). Cell surface glycans are the targets for viral and bacterial infections. Influenza viruses use sialic acid on the cell surface for infection. Sialidase inhibitors such as Tamiflu and Relenza have been developed as anti-influenza drugs. Most of the protein biologics are glycoproteins, and the roles of protein glycans have been revealed in regulation of the functions and glycan-dependent dynamics. Bacterial-derived glycans have been developed as glycan vaccines and vaccine adjuvants. Lipopolysaccharide and the active entity lipid A from Gram negative bacteria activate toll-like receptor 4 (TLR4) to induce strong immune and inflammatory responses. Structural modification of lipid A can alter the activity from high-inflammatory to low-inflammatory. Lipid A derivative 3D-MPL, that moderately activates TLR4 and induces anti-viral responses was developed as an adjuvant for virus vaccines. Self-adjuvanting strategy which uses vaccines conjugated with antigen and adjuvant is also reviewed. A self-adjuvanting vaccine can elicit specific immune response by simultaneous interaction of both an antigen and an adjuvant with the same immune cell. The adjuvant part can recruit the conjugated vaccine to immune cells, activates target immune cells via innate immune receptors, and then facilitates the uptake of the antigen into cells. Application of glycan related drugs is expected for new immunotherapies, anti-inflammatory treatments, regenerative medicine, and diagnostic glycan microarrays, and etc in the near future.
