CARB 21 |
| The selective recognition of carbohydrates under physiological conditions stands as one of the biggest challenges of chemical biology. The potential applications of small oligosaccharide-binding molecules are numerous, and include therapeutic uses such as inhibition of viral and bacterial invasion, diagnosis and selective drug delivery, use as biological probes or analytical biosensors, and supports for affinity purification. Boronic acids are effective as reversible and recoverable receptors for simple monosaccharides. Unfortunately, the currently used boronic acid units often suffer from solubility problems, and they fail to bind non-reducing sugars such as glycopyranosides. Glycopyranosides account for the large majority of biologically important oligosaccharides found in the form of cell-surface glycoconjugates. We focused on identifying new boronic acid units that bind strongly to carbohydrates under aqueous physiological conditions, and eventually develop oligomers of these boronic acids for improved binding potency and higher selectivity. Our results show that 2-(hydroxyalkyl) arylboronic acids stand out as excellent binding agents for monosaccharides, including glucose and fructose, and these highly water-soluble boronic acids also possess the exceptional ability to complex model glycopyranosides. In addition to the measurement of binding constants, further studies were performed to explain the binding selectivity and the binding mode of this unusual class of boronic acids. Preliminary synthetic efforts have yielded conjugatable forms of these boronic acids that can be employed in the design of oligomeric receptors. |
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Carbohydrate Recognition Mechanisms and Applications
9:00 AM-12:15 PM, Tuesday, 28 March 2006 Georgia World Congress Center -- B409, Oral
Division of Carbohydrate Chemistry |