Emerging roles of carbohydrates and glycomimetics in anticancer drug design.
Tumorigenesis is accompanied by marked changes in the expression and presentation of various macromolecules at the cell surface. These tumor-associated adjustments result from the differential expression of genes coding for the production or post-translational modifications of these macromolecules during transformation to a particular tumor phenotype. In turn, tumor cells acquire distinct biophysical properties which set them apart from their normal counterparts. Alterations of carbohydrate structures and their organization on the surface of neoplastic cells is a hallmark of the tumorigenic and, most notably, the metastatic phenotype. Carbohydrate-protein and carbohydrate-carbohydrate interactions are critical events in the progression, dissemination and invasion of cancer cells. Many cell-cell contacts and subsequent remodeling of the tumor microenvironment are mediated by cell-surface glycans. The discovery of agents that modulate these interactions or interfere with the processing of tumor associated oligosaccharides is a fervent area of research today. This review will highlight the current status of the use of carbohydrate-based compounds that are being evaluated as potential anticancer therapeutics. In addition, the use of structures based on glycopeptides and carbohydrate mimetics will also be discussed.
Barchi
J J
JJ
Laboratory of Medicinal Chemistry, Division of Basic Sciences, National Cancer Institute, 37 Convent Dr. MSC4255, Bethesda, MD 20892-4255, USA. barchi@helix.nih.gov
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D050260:Carbohydrate Metabolism; D002240:Carbohydrate Sequence; D002241:Carbohydrates / Q000737:chemistry / Q000494:pharmacology*; D015195:Drug Design; D005947:Glucose / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*
D000970:Antineoplastic Agents; D002241:Carbohydrates; D005947:Glucose