Chemical Synthesis and Antigenicity Evaluation of Shigella dysenteriae Serotype 10 O-Antigen Tetrasaccharide Containing a (S)-4,6-O-Pyruvyl Ketal
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:144 |
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| Enthalten in: |
Journal of the American Chemical Society - 144(2022), 46 vom: 23. Nov., Seite 21068-21079 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Qin, Chunjun [VerfasserIn] |
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| Links: |
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| Themen: |
Epitopes |
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| Anmerkungen: |
Date Completed 24.11.2022 Date Revised 01.12.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1021/jacs.2c05953 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM34868567X |
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| 245 | 1 | 0 | |a 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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| 500 | |a Date Completed 24.11.2022 | ||
| 500 | |a Date Revised 01.12.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 7 | |a Oligosaccharides |2 NLM | |
| 650 | 7 | |a Polysaccharides, Bacterial |2 NLM | |
| 650 | 7 | |a Epitopes |2 NLM | |
| 700 | 1 | |a Li, Lingxin |e verfasserin |4 aut | |
| 700 | 1 | |a Tian, Guangzong |e verfasserin |4 aut | |
| 700 | 1 | |a Ding, Meiru |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Shengyong |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Wuqiong |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Jing |e verfasserin |4 aut | |
| 700 | 1 | |a Seeberger, Peter H |e verfasserin |4 aut | |
| 700 | 1 | |a Yin, Jian |e verfasserin |4 aut | |
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