CARB 23 |
| Natural and recombinant glycoproteins are typically produced as a mixture of heterogeneous glycoforms, from which pure glycoforms are difficult to obtain. Thus, synthesis of homogeneous glycoproteins carrying structurally defined oligosaccharides has become essential both for detailed structure-function relationship studies and for developing glycoprotein-based therapeutics. We describe here a highly convergent chemoenzymatic method for glycopeptide and glycoprotein synthesis. The approach takes advantage of the transglycosylation activity of an endoglycosidase that allows the attachment of a large intact oligosaccharide moiety to a suitable GlcNAc-containing peptide or protein in a single step. It was found that the use of synthetic sugar oxazoline, the mimic of the presumed transition state, as the donor substrate not only expended the substrate availability, but also resulted in a dramatic enhancement of the transglycosylation efficiency to produce large glycopeptides in excellent yield. The extension of the method to glycoprotein synthesis and remodeling will be discussed (1. B. Li et al, J. Am. Chem. Soc., 2005, 127, 9692; 2. H. Li et al, J. Org. Chem., 2005, 70, 9990; 3. L. X. Wang et al, ChemBioChem, 2005, 6, 1068; 4. Y. Zeng et al, Chemistry Eur. J., 2006, 12, 3355). |
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Chemical Glycobiology Symposium
9:00 AM-12:20 PM, Monday, 11 September 2006 Hilton San Francisco -- Yosemite C, Oral
Division of Carbohydrate Chemistry |