Synthesis and antigenicity of BBGL-2 glycolipids of Borrelia burgdorferi, the causative agent of Lyme disease

Abstract

Borrelia burgdorferi is the etiological agent for Lyme disease (LD), the most common vector borne disease in the United States. There is no human vaccine against LD currently available. Our approach to a vaccine is based on its surface-exposed glycolipids. One group of these glycolipids termed BBGL-2 consists of 1,2-di-O-acyl-3-O-(α-D-galactopyranosyl)-sn-glycerol congeners having palmitic, oleic, stearic, linoleic, and myristic acids. In order to delineate the immunodominant region(s) of the BBGL-2 components, we embarked on a synthetic project to provide available structurally defined, homogeneous analogs of BBGL-2 that might help identify the best vaccine candidate. The antigenicity of the synthetic glycolipids was examined by dot-blot analysis using mice sera obtained by immunization with killed B. burgdorferi cells, with native BBGL-2 in complete Freund's adjuvant, as well as sera obtained from patients with Lyme disease. We found that the presence of two acyl groups in the glycerol moiety was essential for antigenicity. At least one of these groups must be an oleoyl moiety. Neither the anomeric configuration of the galactose nor the configuration of the glycerol at C-2 was a decisive factor. Based on these findings we designed an `unnatural' BBGL-2 analog having the structure 3-O-(β-D-galactopyranosyl)-1,2-di-O-oleoyl-DL-glycerol which is easier and less expensive to synthesize than the other BBGL-2 congeners prepared in this study. This substance proved to be antigenic and is considered a candidate vaccine for Lyme disease.

CD1b presents self and Borrelia burgdorferi diacylglycerols to human T cells

“…To characterize in‐house produced synthetic BbGL‐II (1, 2 di‐ O ‐oleoyl‐3‐ O ‐α‐ d ‐galactopyranosyl‐ sn ‐glycerol) , we carried out positive mode, multistage collision‐induced dissociation (CID)–electrospray ionization (ESI)–mass spectrometry (MS) (Fig. ).…”

Synthetic Oligosaccharides as Tools to Demonstrate Cross-Reactivity between Polysaccharide Antigens

“…The methods used for 1D and 2D NMR data acquisition were similar to those reported by us recently for a set of glycolipids. 36 …”

Total Synthesis and Structure-Activity Relationship of Glycoglycerolipids from Marine Organisms

“…Compared with galactosyl bromides [67], the trichloroacetimidate methodology of glycosylation developed by Schmidt [68], which allowed reaction with chiral 1,2- O -isopropylidene- sn -glycerol without racemization, was also common in the synthesis of glycoglycerolipids [66,69,70]. Lafont et al .…”