PMID: 7538869Nov 1, 1994Paper

Modulation of antibody affinity by synthetic modifications of the most exposed pyranose residue of a trisaccharide epitope

Bioorganic & Medicinal Chemistry
D R Bundle, E Eichler

Abstract

When the Salmonella trisaccharide epitope, methyl 3-O-(3,6-dideoxy-alpha-D-xylo-hexopyranosyl)-2-O-(alpha-D-galactopyra nos yl)- alpha-D-mannopyranoside 12 is bound by a monoclonal antibody Se155.4, the 3,6-dideoxy-alpha-D-hexose is completely buried, while the galactopyranosyl mannopyranosyl units lay across the protein surface. Crystallography of an antibody complexed with 12 also shows that the galactose residue is the most exposed saccharide. A simplified strategy to synthesize 12 and analogues modified at the galactose residue is described. Monosaccharide building blocks containing benzyl ether and ester protecting groups were used for efficient assembly of trisaccharides that can be deprotected by a single hydrogenolysis step, or occasionally preceded by a transesterification stage. Glycosylation of methyl 2-O-benzoyl-4,6-di-O-benzyl-alpha-D- mannopyranoside 4 by 2,4-di-O-benzyl-3,6-dideoxy-D-xylo-hexopyranosyl chloride 8 affords after transesterification the disaccharide acceptor 10. This disaccharide serves as a universal acceptor for glycosylation by glycosyl donors that lead, following facile deprotection, to the alpha- and beta-D-galacto, alpha- and beta-D-gluco, and 2-amino-2-deoxy-alpha-D-galacto trisaccharides 12,...Continue Reading

References

Oct 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·C J HonsikR A Reisfeld
Oct 1, 1988·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·S Vadhan-RajA N Houghton
Mar 1, 1966·Bacteriological Reviews·O LüderitzO Westphal
Dec 23, 1983·Carbohydrate Research·B M Pinto, D R Bundle
Jan 1, 1983·Acta Chemica Scandinavica. Series B: Organic Chemistry and Biochemistry·K Bock, M Meldal
Jul 5, 1994·Proceedings of the National Academy of Sciences of the United States of America·A ZdanovM Cygler

❮ Previous
Next ❯