CARB 99 |
| Addition of carbohydrates and/or lipids to drugs offers opposing avenues to greatly alter their physicochemical properties.[1] In concert, glycolipids are an important class of bioactive compounds. Recently, we have described a "click-tailing" approach to a family of glycosylated benzenesulfonamides that display isozyme discrimination among the carbonic anhydrase (CA) family of enzymes.[2] The carbohydrate moiety should also improve aqueous solubility and decrease membrane permeability allowing the targeting of extracellular binding sites of CA isozymes overexpressed in solid tumors. In a complementary approach, we have also synthesized lipid derivatives of aminoglycosides using highly selective chemistry on these complex systems.[3] This modification was designed to improve membrane permeability against the waxy coat of Mycobacterium tuberculosis. Biological testing results on both sets of compounds will be discussed. [1] Blanchfield, J.; Toth, I. Curr. Med. Chem. 2004, 11, 2375. [2] Wilkinson, B. L.; Bornaghi, L. F.; Houston, T. A.; Innocenti, A.; Supuran, C. T.; Poulsen, S.-A. J. Med. Chem. 2006, 49, 6539. [3] Quader, S.; Boyd, S. E.; Jenkins, I. D.; Houston, T. A. Org. Biomol.Chem. 2006, 4, 36. |
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Nucleic Acid Therapeutics
9:00 AM-11:45 AM, Wednesday, March 28, 2007 McCormick Place North -- Room N226, Level 2, Oral
Division of Carbohydrate Chemistry |