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Chemical synthesis and antigenicity evaluation of Shigella dysenteriae serotype 10 O-antigen tetrasaccharide containing a (S)-4,6-O-pyruvyl ketal

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Qin,  Chunjun
Peter H. Seeberger - Vaccine Development, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

Tian,  Guangzong
Peter H. Seeberger - Vaccine Development, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Seeberger,  Peter H.       
Peter H. Seeberger - Vaccine Development, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society;

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Citation

Qin, C., Li, L., Tian, G., Ding, M., Zhu, S., Song, W., et al. (2022). Chemical synthesis and antigenicity evaluation of Shigella dysenteriae serotype 10 O-antigen tetrasaccharide containing a (S)-4,6-O-pyruvyl ketal. Journal of the American Chemical Society, 144(46), 21068-21079. doi:10.1021/jacs.2c05953.


Cite as: https://hdl.handle.net/21.11116/0000-000B-7048-6
Abstract
Shigella is the second most common etiologic pathogen responsible for childhood acute diarrhea. An anti-Shigella vaccine is still eagerly awaited due to the increasing drug resistance of this pathogen. The Shigella O-antigen is a promising vaccine target. To identify the immune epitopes of the glycan, the first total synthesis of Shigella dysenteriae serotype 10 O-antigen tetrasaccharide containing a (S)-4,6-O-pyruvyl ketal was completed. The 1,2-trans-β-glycosylation & C2 epimerization and conformational locking strategies facilitated the construction of two 1,2-cis-β-glycosidic linkages. The reactivities of both the glycosyl donor and acceptor were improved by adding electron-donating benzyl groups, enabling an efficient assembly of the tetrasaccharide. The (S)-4,6-O-pyruvyl ketal was introduced at the final stage due to its influence on the glycosylation stereospecificity and efficiency. In addition, (R)-4,6-O-pyruvylated and nonpyruvylated tetrasaccharides and three further fragments were synthesized. Glycan microarray screening revealed that the tetrasaccharide repeating unit is the key antigenic epitope of the O-antigen. Moreover, the (S)-4,6-O-pyruvyl ketal is an essential structural feature of this antigen for designing carbohydrate-based vaccines against S. dysenteriae serotype 10. The comparison of the (S)-4,6-O-pyruvylated glycan and its (R)-epimer will set an example for biological evaluation of other bacterial glycans containing pyruvyl ketals.