Several examples of bioisosteric modifications to carbohydrates have been reported this review aims to consolidate them and presents different possibilities for enhancing core interactions in glycomimetics.Ĭancer cells of diverse origins express extracellular tumor-specific carbohydrate antigens (TACAs) because of aberrant glycosylation. These changes can offer improvements to both binding affinity (e.g., reduced desolvation costs, enhanced metal chelation) and pharmacokinetic parameters (e.g., improved oral bioavailability). A related approach to developing glycomimetics relies on the bioisosteric replacement of carbohydrate functional groups. Several strategies have been developed for glycomimetic design such as ligand pre-organization or reducing polar surface area. Glycomimetic compounds, which mimic the structure and function of native glycans, have been successful in producing molecules with improved pharmacokinetic (PK) and pharmacodynamic (PD) features. Although these interactions are highly specific, native carbohydrates are characterized by very low affinities and inherently poor pharmacokinetic properties.
These altered glycan structures represent a target for novel therapies by modulating their associated interactions with neighboring cells and molecules. The aberrant presentation of carbohydrates has been linked to a number of diseases, such as cancer metastasis and immune dysregulation. This review will present a summary of efforts and advancements made to date on creating carbohydrate-based anticancer vaccines, and will include novel approaches to overcoming the poor immunogenicity of carbohydrate-based vaccines. In order to enhance their immunogenicity and promote long-lasting immune responses, carbohydrates are often chemically modified to link to an immunogenic protein or peptide fragment for eliciting T-cell-dependent responses. Unfortunately, carbohydrates alone evoke poor immunogenicity, owing to their lack of ability in inducing T-cell-dependent immune responses.
Many tumor antigens (e.g., GM2, Le(y), globo H, sialyl Tn and TF) have been identified to date in a variety of cancers. Cancer cells can often be distinguished from healthy cells by the expression of unique carbohydrate sequences decorating the cell surface as a result of aberrant glycosyltransferase activity occurring within the cell these unusual carbohydrates can be used as valuable immunological targets in modern vaccine designs to raise carbohydrate-specific antibodies.
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