Dataset Information

Synthesis of ?-C-GlcNAc Ser from ?-C-Glc Ser.

ABSTRACT: The glycosylation of proteins, specifically installation of O-GlcNAc on Ser/Thr residues, is a dynamic control element for transcription repression, protein degradation, and nutrient sensing. To provide homogeneous and stable structures with this motif, the synthesis of a C-linked mimic, C-GlcNAc Ser, has been prepared from the C-Glc Ser by a double inversion strategy using azide to insert the C-2 nitrogen functionality. The C-Glc Ser was available by a ring-closing metathesis and hydroalkoxylation route.

SUBMITTER: Nolen EG

PROVIDER: S-EPMC3736601 | biostudies-literature | 2013 Jul

REPOSITORIES: biostudies-literature

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Publications

Synthesis of β-C-GlcNAc Ser from β-C-Glc Ser.

Nolen Ernest G EG Li Leyan L Waynant Kristopher V KV

The Journal of organic chemistry 20130617 13

The glycosylation of proteins, specifically installation of O-GlcNAc on Ser/Thr residues, is a dynamic control element for transcription repression, protein degradation, and nutrient sensing. To provide homogeneous and stable structures with this motif, the synthesis of a C-linked mimic, C-GlcNAc Ser, has been prepared from the C-Glc Ser by a double inversion strategy using azide to insert the C-2 nitrogen functionality. The C-Glc Ser was available by a ring-closing metathesis and hydroalkoxylat ...[more]

PMID: 23767880

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Project description:The protozoan parasite, Trypanosoma cruzi, the etiologic agent of Chagas disease (ChD), has a cell surface covered by immunogenic glycoconjugates. One of the immunodominant glycotopes, the trisaccharide Gal?(1,3)Gal?(1,4)GlcNAc?, is expressed on glycosylphosphatidylinositol-anchored mucins of the infective trypomastigote stage of T. cruzi and triggers high levels of protective anti-?-Gal antibodies (Abs) in infected individuals. Here, we have efficiently synthesized the mercaptopropyl glycoside of that glycotope and conjugated it to maleimide-derivatized bovine serum albumin (BSA). Chemiluminescent-enzyme-linked immunosorbent assay revealed that Gal?(1,3)Gal?(1,4)GlcNAc?-BSA is recognized by purified anti-?-Gal Abs from chronic ChD patients ?230-fold more strongly than by anti-?-Gal Abs from sera of healthy individuals (NHS anti-?-Gal). Similarly, the pooled sera of chronic Chagas disease patients (ChHSP) recognized Gal?(1,3)Gal?(1,4)GlcNAc? ?20-fold more strongly than pooled NHS. In contrast, the underlying disaccharide Gal?(1,4)GlcNAc? and the monosaccharide GlcNAc? or GlcNAc? conjugated to BSA are poorly or not recognized by purified anti-?-Gal Abs or sera from Chagasic patients or healthy individuals. Our results highlight the importance of the terminal Gal? moiety for recognition by Ch anti-?-Gal Abs and the lack of Abs against nonself Gal?(1,4)GlcNAc? and GlcNAc? glycotopes. The substantial difference in binding of Ch vs. NHS anti-?-Gal Abs to Gal?(1,3)Gal?(1,4)GlcNAc?-BSA suggests that this neoglycoprotein (NGP) might be suitable for experimental vaccination. To this end, the Gal?(1,3)Gal?(1,4)GlcNAc?-BSA NGP was then used to immunize ?1,3-galactosyltransferase-knockout mice, which produced antibody titers 40-fold higher as compared with pre-immunization titers. Taken together, our results indicate that the synthetic Gal?(1,3)Gal?(1,4)GlcNAc? glycotope coupled to a carrier protein could be a potential diagnostic and vaccine candidate for ChD.

Dataset Information

Synthesis of ?-C-GlcNAc Ser from ?-C-Glc Ser.

Publications

Synthesis of β-C-GlcNAc Ser from β-C-Glc Ser.

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