The long term objectives of this proposal are to identify and characterize cellular receptors for specific oligosaccharide, and to use this information to target therapeutic agents (e.g. proteins) to specific cells. during the Phase I funding period methods to purify high mannose oligosaccharide were developed. In Phase II these oligosaccharide will be used for three purposes, including: 1) Preparation of neoglycoproteins for targeting to specific cells; 2) Characterization of receptors on immune system cells, and for studying binding to macrophage; and 3) As model compounds to develop and evaluate new methods for oligosaccharide structural analysis. Technology for purifying individual high mannose oligosaccharide isomers in quantity will be developed, and methods for coupling these individual oligosaccharide to specific protein amino acids will be explored. Binding of the individual oligosaccharide isomers to the macrophage receptor binding specificity. The three- dimensional structure of the oligosaccharide isomers will be determine by a combination of NMR and computer modelling studies, and related to the receptor binding patterns.
| Davis, J T; Hirani, S; Bartlett, C et al. (1994) 1H NMR studies on an Asn-linked glycopeptide. GlcNAc-1 C2-N2 bond is rigid in H2O. J Biol Chem 269:3331-8 |
