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

• Shuo Zhang,
• Ondřej Daněk and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2026, 22, 821–827, doi:10.3762/bjoc.22.64

• 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

• . Keywords: glycoconjugate vaccines; glycosylation; oligosaccharides; selectivity control; total synthesis; Introduction The emergence and rapid spread of multidrug-resistant bacteria represent a critical threat to global health [1][2][3][4]. Among these pathogens, Klebsiella pneumoniae has surfaced as a

• host immune defenses and enhances tolerance to antibiotic treatment [14][15][16]. As a major virulence factor, CPS can trigger specific adaptive immune responses, rendering these glycans attractive targets for vaccine development [17][18]. Glycoconjugate vaccines that are constructed by covalently

Chemical glycobiology

• Elisa Fadda,
• Rachel Hevey,
• Benjamin Schumann and
• Ulrika Westerlind

Beilstein J. Org. Chem. 2025, 21, 8–9, doi:10.3762/bjoc.21.2

• on any other biomolecule, dating back to the time of Emil Fischer and the elucidation of monosaccharide structures [1]. Later, foundational contributions came in the form of the first glycoconjugate vaccines [2][3], the elucidation of the blood group system [4], and many others. Among these, we dare

Synthesis of Streptococcus pneumoniae serotype 9V oligosaccharide antigens

• Sharavathi G. Parameswarappa,
• Claney L. Pereira and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2020, 16, 1693–1699, doi:10.3762/bjoc.16.140

• developing countries [3]. With increasing antimicrobial resistance to antibiotics, vaccines are becoming even more important to control these pathogens. Despite the availability of multivalent polysaccharide and glycoconjugate vaccines such as Pneumovax, Prevnar® 13, and Synflorix, pneumonococcal diseases

• Chemistry and Biochemistry, Arnimallee 22, 14195 Berlin, Germany 10.3762/bjoc.16.140 Abstract Streptococcus pneumoniae (SP) bacteria cause serious invasive diseases. SP bacteria are covered by a capsular polysaccharide (CPS) that is a virulence factor and the basis for SP polysaccharide and glycoconjugate

• vaccines. The serotype 9V is part of the currently marketed conjugate vaccine and contains an acetate modification. To better understand the importance of glycan modifications in general and acetylation in particular, defined oligosaccharide antigens are needed for serological and immunological studies

Total synthesis of a Streptococcus pneumoniae serotype 12F CPS repeating unit hexasaccharide

• Peter H. Seeberger,
• Claney L. Pereira and
• Subramanian Govindan

Beilstein J. Org. Chem. 2017, 13, 164–173, doi:10.3762/bjoc.13.19

• with 85% [17]. In order to improve current glycoconjugate vaccines additional serotypes such as 12F should be included in next-generation preparations [18]. Synthetic oligosaccharides are important tools for the identification of vaccine epitopes and have been the key to the creation of monoclonal

• immunological analysis of S. pneumoniae serotype 12F can be undertaken, and future work will address the expanded inclusion of this antigen in next-generation glycoconjugate vaccines. Abbreviations Ac: acetate ester; BAIB: bis(acetoxy)iodobenzene; Bz: benzoyl; CPS: capsular polysaccharide; DMF: N,N

• better immunological understanding of the epitopes that protect from bacterial infection requires defined oligosaccharides obtained by total synthesis. The key to the synthesis of the S. pneumoniae serotype 12F CPS hexasaccharide repeating unit that is not contained in currently used glycoconjugate

Synthesis and immunological evaluation of protein conjugates of Neisseria meningitidis X capsular polysaccharide fragments

• Laura Morelli,
• Damiano Cancogni,
• Marta Tontini,
• Alberto Nilo,
• Sara Filippini,
• Paolo Costantino,
• Maria Rosaria Romano,
• Francesco Berti,
• Roberto Adamo and
• Luigi Lay

Beilstein J. Org. Chem. 2014, 10, 2367–2376, doi:10.3762/bjoc.10.247

• another key parameter which has been shown to deeply affect the immunogenicity of glycoconjugate vaccines [42][43]. In the present preliminary study, glycoconjugates with moderate loading were compared. It has been reported for other bacterial systems that the immunogenicity of short oligosaccharides can

Efficient routes toward the synthesis of the D-rhamno-trisaccharide related to the A-band polysaccharide of Pseudomonas aeruginosa

• Aritra Chaudhury,
• Sajal K. Maity and
• Rina Ghosh

Beilstein J. Org. Chem. 2014, 10, 1488–1494, doi:10.3762/bjoc.10.153

• tetrasaccharide, α-D-Rhap-(1→2)-α-D-Rhap-(1→3)-α-D-Rhap-(1→3)-α-D-Rhap [17] and a trisaccharide, α-D-Rhap-(1→3)-α-D-Rhap-(1→2)-α-D-Rhap [18] related to the A-band polysaccharide of P. aeruginosa were made with a view to develop glycoconjugate vaccines, but none have ultimately materialized into valid vaccine

Biosynthesis of rare hexoses using microorganisms and related enzymes

• Zijie Li,
• Yahui Gao,
• Hideki Nakanishi,
• Xiaodong Gao and
• Li Cai

Beilstein J. Org. Chem. 2013, 9, 2434–2445, doi:10.3762/bjoc.9.281

• ideal starting material for glycoconjugate vaccines against the enteropathogenic bacterium Shigella sonne [80]. Enzymatically, L-glucose can be synthesized by isomerizing L-fructose (Scheme 13) catalyzed by D-xylose isomerase from Candida utilis [81] or whole cells of a mutant Klebsiella pneumoniae

Synthesis of 6-PEtN-α-D-GalpNAc-(1–>6)-β-D-Galp-(1–>4)-β-D-GlcpNAc-(1–>3)-β-D-Galp-(1–>4)-β-D-Glcp, a Haemophilus influenzae lipopolysacharide structure, and biotin and protein conjugates thereof

• Andreas Sundgren,
• Martina Lahmann and
• Stefan Oscarson

Beilstein J. Org. Chem. 2010, 6, 704–708, doi:10.3762/bjoc.6.80

• carbohydrate surface antigens in glycoconjugate vaccines can be considered and investigated. One such suggested structure from Haemophilus influenzae LPS is the phosphorylated pentasaccharide 6-PEtN-α-D-GalpNAc-(1→6)-β-D-Galp-(1→4)-β-D-GlcpNAc-(1→3)-β-D-Galp-(1→4)-β-D-Glcp. Results: Starting from a spacer

• proven to be highly effective [2]. These vaccines are glycoconjugate vaccines, based on capsular poly- or oligosaccharide structures, either native or synthetic [3][4], linked to a carrier protein. The lipopolysaccharide (LPS) of H. influenzae shows a huge structural variety and hence non-capsulated