Work

Total synthesis of the capsular polysaccharide repeating unit towards the development of a glycoconjugate vaccine against Klebsiella pneumoniae ST512

Year: 2026

Type: article

Abstract: Klebsiella pneumoniae ST512 is an emerging multidrug-resistant pathogen whose capsular polysaccharide represents a prime target for vaccine development. Here, we report the first total synthesis of the branched hexasaccharide repeating unit of the K. pneumoniae ST512 CPS, together with four structurally related oligosaccharide analogues. Key synthetic challenges including the stereoselective construction of the 1,2- cis glycosidic linkage on the galacturonic acid core and the inherently low reactivity of elongated oligosaccharide intermediates were addressed employing orthogonally protected building blocks. The resulting library of conjugation-ready oligosaccharides, equipped with aminopentyl linkers, enables glycan microarray-based identification of minimal immunogenic epitopes. This work establishes a robust chemical foundation for the rational development of semi-synthetic glycoconjugate vaccines targeting K. pneumoniae ST512.

Source: Beilstein Journal of Organic Chemistry

DOI: 10.3762/bjoc.22.64

Authors: Shuo Zhang, Ondřej Daněk, Peter H Seeberger

Institutions: Dalian University of Technology, Max Planck Institute of Colloids and Interfaces, Freie Universität Berlin, Czech Academy of Sciences, Institute of Organic Chemistry and Biochemistry

Language: English

Topic: Carbohydrate Chemistry and Synthesis

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: diamond

Funder: Max-Planck-Gesellschaft