A Bioactive Synthetic Outer-Core Oligosaccharide Derived from a Klebsiella pneumonia Lipopolysaccharide for Bacteria Recognition

被引：2

作者：

Chen, Dushen ^{[1
]}

Srivastava, Akhilesh. K. K. ^{[2
]}

Dubrochowska, Justyna ^{[1
]}

Liu, Lin ^{[3
]}

Li, Tiehai ^{[3
]}

Hoffmann, Joseph. P. P. ^{[2
]}

Kolls, Jay. K. K. ^{[2
]}

Boons, Geert-Jan ^{[1
,3
,4
,5
]}

机构：

[1] Univ Utrecht, Utrecht Inst Pharmaceut Sci, Dept Chem Biol & Drug Discovery, NL-3584 CG Utrecht, Netherlands

[2] Tulane Sch Med, Dept Med & Pediat, New Orleans, LA USA

[3] Univ Georgia, Complex Carbohydrate Res Ctr, Athens, GA 30602 USA

[4] Univ Utrecht, Bijvoet Ctr Biomol Res, Utrecht, Netherlands

[5] Univ Georgia, Chem Dept, Athens, GA 30602 USA

来源：

CHEMISTRY-A EUROPEAN JOURNAL | 2023年 / 29卷 / 25期

基金：

美国国家卫生研究院;

关键词：

conjugation; glycoconjugate; glycosylation; oligosaccharides; vaccine; STEREOSELECTIVE-SYNTHESIS; REGION; POLYSACCHARIDE; PART; IDENTIFICATION; EPIDEMIOLOGY;

D O I：

10.1002/chem.202203408

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

There is an urgent need for new treatment options for carbapenem-resistant Klebsiella pneumoniae (K. pneumoniae), which is a common cause of life-threatening hospital- and community-acquired infections. Prophylactic or therapeutic vaccination may offer an approach to control these infections, however, none has yet been approved for human use. Here, we report the chemical synthesis of an outer core tetra- and pentasaccharide derived from the lipopolysaccharide of K. pneumoniae. The oligosaccharides were equipped with an aminopentyl linker, which facilitated conjugation to the carrier proteins CRM197 and BSA. Mice immunized with the glycoconjugate vaccine candidates elicited antibodies that recognized isolated LPS as well as various strains of K. pneumoniae. The successful preparation of the oligosaccharides relied on the selection of monosaccharide building blocks equipped with orthogonal hydroxyl and amino protecting groups. It allowed the differentiation of three types of amines of the target compounds and the installation of a crowded 4,5-branched Kdo moiety.

引用

页数：11