Carbohydrate-based experimental therapeutics for cancer, HIV/AIDS and other diseases

Abstract

This review, primarily for general readers, briefly presents experimental approaches to therapeutics of cancer, HIV/AIDS and various other diseases based on advances in glycobiology and glycochemistry. Experimental cancer and HIV/AIDS vaccines are being developed in attempts to overcome weak immunological responses to carbohydrate-rich surface antigens using carriers, adjuvants and novel carbohydrate antigen constructs. Current carbohydrate-based vaccines are used for typhus, pneumonia, meningitis; vaccines for anthrax, malaria and leishmaniasis are under development. The link between O-linked beta-N-acetylglucosamine glycosylation and protein phosphorylation in diseases including diabetes and Alzheimer's disease is also explored. Carbohydrate-associated drugs that are in current use or under development, such as heparan sulfate binders, lectins, acarbose, aminoglycosides, tamiflu and heparin, and technologies using carbohydrate and lectin microarrays that offer improved diagnostic and drug development possibilities, are described. Advances in carbohydrate synthesis, analysis and manipulation through the emerging fields of glycochemistry and glycobiology are providing new approaches to disease therapeutics.

Figure 1

HIV surrounded by mannose-rich carbohydrate. Not intended to be structurally accurate. The figure is intended to show that therapeutic approaches to this disease must contend with a carbohydrate coat consisting of host glycans.

Figure 2

A.Glycosylation (G) versus B. phosphorylation (P) that can occur on some serine (S) and threonine (T) residues of the proteins.

Figure 3

Carbohydrate microarray. Protein, cell or antibody ( X ) coupled to a label ( W ) is incubated with the carbohydrate microarray that contains sugars ( A-H ) covalently attached ( Y ) to a glass slide or other substrate ( Z ) to determine to which sugar(s) the labeled entity binds.