Synthesis of spacer-containing chlamydial disaccharides as analogues of the α-Kdop-(2→8)-α-Kdop-(2→4)-α-Kdop trisaccharide epitope

On the basis of high-resolution crystal structures of the antigen binding fragment of the chlamydia-specific monoclonal antibody S25-2 in complex with the trisaccharide α-Kdop-(2→8)-α-Kdop-(2→4)-α-Kdop and part structures thereof, seven modified α-Kdop-(2→8)-α-Kdop disaccharide derivatives were synthesized starting from the protected disaccharide allyl ketoside 1. Hydroboration and subsequent oxidation as well as ozonolysis, respectively, followed by Wittig-reaction for chain elongation were used to install a terminal carboxylic group on spacer entities of various chain lengths. Furthermore, addition of methyl 2-thioacetate to the allyl group furnished the corresponding thioether derivative. Standard deprotection gave the target disaccharides as simplified trisaccharide analogues, which will be used to probe the contribution of the proximal carboxylic group in the binding of chlamydia-specific di- and trisaccharide-reactive monoclonal antibodies.

The chemical synthesis of Kdo disaccharide spacer glycosides containing a terminal carboxyl group is described.Figure optionsDownload as PowerPoint slide