Citation: Guochao Lv, Guangzong Tian, Guodong Chen, Shengyong Zhu, Jialong Bao, Chunjun Qin, Xiaopeng Zou, Jing Hu, Peter H. Seeberger, Jian Yin. Chemical synthesis of the highly functionalized O-antigen repeating unit from Pseudomonas aeruginosa serotype O3 for glycoconjugate vaccine development[J]. Chinese Chemical Letters, ;2026, 37(2): 111875. doi: 10.1016/j.cclet.2025.111875 shu

Chemical synthesis of the highly functionalized O-antigen repeating unit from Pseudomonas aeruginosa serotype O3 for glycoconjugate vaccine development

Guochao Lv ^{a, e, 1} ,
Guangzong Tian ^{a, e, 1} ,
Guodong Chen ^{a, b, e} ,
Shengyong Zhu ^{a, b, e} ,
Jialong Bao ^{a, e} ,
Chunjun Qin ^{a, e, f} ,
Xiaopeng Zou ^{a, e} ,
Jing Hu ^{c, e, f} ,
Peter H. Seeberger ^b ,
Jian Yin ^{a, d, e, *,}

a.
School of Biotechnology and Key Laboratory of Carbohydrate Chemistry and Biotechnology of Ministry of Education, Jiangnan University, Wuxi 214122, China
b.
Biomolecular Systems Department, Max Planck Institute of Colloids and Interfaces, Potsdam 14476, Germany
c.
Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China
d.
School of Life Sciences and Health Engineering, Jiangnan University, Wuxi 214122, China
e.
Innovation Center for Vaccine Engineering, Jiangnan University, Wuxi 214122, China
f.
Institute of Future Food Technology, JITRI, Yixing 214200, China

jianyin@jiangnan.edu.cn

Received Date: 20 August 2025
Revised Date: 19 September 2025
Accepted Date: 22 September 2025
Available Online: 23 September 2025

Figures(8)

Pseudomonas aeruginosa is an opportunistic pathogen responsible for severe nosocomial infections. This multidrug-resistant bacterium can cause pneumonia and cystic fibrosis, both of which are associated with high morbidity and mortality rates. The lipopolysaccharide of P. aeruginosa serves as an attractive target for the development of effective glycoconjugate vaccines. In this article, we report the first chemical synthesis of the highly challenging tetrasaccharide repeating unit of the P. aeruginosa serotype O3 O-antigen using a two-directional [1+(2 + 1)] glycosylation strategy. The synthesis is particularly challenging due to the poor nucleophilicity of the axial C4 hydroxyl group of L-galactose and the steric hindrance imposed by the 3S-hydroxybutyryl (Hb) chain. Furthermore, the presence of an acetyl group at the ortho position relative to the glycosylation site on L-galactose can lead to undesirable acetyl migration. Additionally, it is noteworthy that the selective removal of a 2-naphthylmethyl ether (Nap) during the late stages of synthesis, particularly in the presence of multiple benzyl groups, can be somewhat challenging to predict. Through the careful selection of synthetic strategies, building blocks, and optimized reaction conditions, we achieved the stereoselective glycosylations, selective oxidation of primary alcohols, remarkable enhancement of acceptor activity, and efficient introduction of the 3S-Hb group. The synthetic methodology presented in this work serves as a valuable reference for the preparation of structurally related oligosaccharides. By incorporating an aminopropyl linker, the target tetrasaccharide facilitates glycan microarray preparation and in vivo immunological assessments, thereby accelerating progress toward a synthetic glycoconjugate vaccine for P. aeruginosa.
- Chemical synthesis,
- Pseudomonas aeruginosa,
- Lipopolysaccharide,
- Steric hindrance,
- Poor nucleophilicity,
- Acetyl migration,
- Glycoconjugate vaccines
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