Mutant glycosyltransferases assist in linking glycoconjugates via glycan chains: Development of a targeted drug delivery system and contrast agents for MRI

BIOT 185

Pradman Krishen Qasba, qasba@helix.nih.gov, Structural Glycobiology Section, Nanobiology Program, Center for Cancer Research, NCI-Frederick, NCI, NIH, P.O Box B, Bldg. 469, Rm 221, NCI-Frederick, Frederick, MD 21702-1203, Elizabeth Boeggeman, eeb@helix.nih.gov, Structural Glycobiology Section, Nanobiology Program, Center for Cancer Research, SAIC, Inc., NCI-Frederick, NCI, NIH, P.O Box B, Bldg. 469, Rm 221, NCI-Frederick, Frederick, MD 21702-1203, and Boopathy Ramakrishnan, Structural Glycobiology Section, Nanobiology Program, Center for Cancer Research, SAIC, Inc. NCI-Frederick, NCI, NIH, P.O Box B, Bldg. 469, Rm 221, NCI-Frederick, Frederick, MD 21702-1203.
The structural information of glycosyltransferases has revealed that the specificity of the sugar donor in these enzymes is determined by a few residues in the sugar-nucleotide binding pocket of the enzyme, conserved among the family members from different species. This in turn has made it possible to reengineer the existing glycosyltransferases with broader sugar donor specificities. Mutation of these residues generates novel glycosyltransferases that can transfer a sugar residue with a chemically reactive functional group to N-acetylglucosamine (GlcNAc), galactose (Gal) and xylose residues of glycoproteins, glycolipids and proteoglycans (glycoconjugates). The potential of mutant glycosyltransferases to produce glycoconjugates carrying sugar moieties with reactive groups which can be used subsequently in the assembly of bio-nanoparticles is making it possible to develop a targeted-drug delivery system and contrast agents for MRI. This project has been funded in whole or in part with federal funds from the NCI, National Institutes of Health, under contract N01-CO-12400.
 

Biophysical and Biomolecular Symposium: Targeted Delivery of Proteins & Nucleotides
8:00 AM-11:00 AM, Wednesday, August 22, 2007 BCEC -- 107 A/B, Oral

Division of Biochemical Technology

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007