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

Dushen Chen; Akhilesh K Srivastava; Justyna Dubrochowska; Lin Liu; Tiehai Li; Joseph P Hoffmann; Jay K Kolls; Geert-Jan Boons

doi:10.1002/chem.202203408

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

Dushen Chen
, Akhilesh K Srivastava
, Justyna Dubrochowska
, Lin Liu
, Tiehai Li
, Joseph P Hoffmann
, Jay K Kolls
, Geert-Jan Boons

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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.

Original language	English
Article number	e202203408
Number of pages	11
Journal	Chemistry-A European Journal
Volume	29
Issue number	25
Early online date	20 Jan 2023
DOIs	https://doi.org/10.1002/chem.202203408
Publication status	Published - 2 May 2023

Bibliographical note

Funding Information:
The research was supported by grants from the Netherlands Organization for Scientific Research (TOP‐PUNT 718.015.003 to G.J.B.), the National Institutes of Health (R35HL139930 and R01AI120033 to J.K.K.), and the Louisiana Board of Regents Endowed Chairs for Eminent Scholars program (to J.K.K). D.C. was supported by a scholarship from the Chinese Scholarship Council (CSC).

Publisher Copyright:
© 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

conjugation
glycoconjugate
glycosylation
oligosaccharides
vaccine

Access to Document

10.1002/chem.202203408Licence: CC BY-NC-ND

Chemistry A European J - 2023 - Chen - A Bioactive Synthetic Outer‐Core Oligosaccharide Derived from a Klebsiella pneumoniaFinal published version, 3.46 MBLicence: CC BY-NC-ND

Cite this

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abstract = "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.",

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note = "Funding Information: The research was supported by grants from the Netherlands Organization for Scientific Research (TOP‐PUNT 718.015.003 to G.J.B.), the National Institutes of Health (R35HL139930 and R01AI120033 to J.K.K.), and the Louisiana Board of Regents Endowed Chairs for Eminent Scholars program (to J.K.K). D.C. was supported by a scholarship from the Chinese Scholarship Council (CSC). Publisher Copyright: {\textcopyright} 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.",

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AU - Li, Tiehai

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AU - Kolls, Jay K

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