Doctor of Philosophy, University of Alberta (2009)
Jianghong Rao, Postdoctoral Faculty Sponsor
Synthesis of modified Trichinella spiralis disaccharide epitopes and a comparison of their recognition by chemical mapping and saturation transfer difference NMR
2014; 383: 1-13
A rat monoclonal antibody 9D4 raised against the cell surface N-glycan of the parasite Trichinella spirallis protects rats against further infection. The terminal disaccharide β-d-Tyvp(1→3)β-d-GalNAcp (2) represents the immunodominant portion of the antigenic determinant. Chemical mapping of the antibody binding site by functional group modification employing monodeoxy and mono-O-methyl congeners identified key polar contacts and topography of the bound disaccharide. We report here a comparison of the chemical mapping studies with the antigen topography inferred from saturation transfer difference (STD) NMR experiments. During chemical mapping several congeners of compound 2 showed substantially enhanced binding. Pairing of these functional group modifications to create derivatives 6 and 7 did not show additive free energy gains and STD NMR data point to small variations in mode of binding as a probable cause. Improved syntheses of disaccharides 2-7 are reported.
View details for DOI 10.1016/j.carres.2013.10.012
View details for Web of Science ID 000328745400001
View details for PubMedID 24239604