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Klebsiella pneumoniae (KP) is a common opportunistic pathogen that emerged as a new critical threat to human health, due to its hypervirulence and widespread resistance against many antibiotics, including carbapenems. Alternative intervention strategies such as vaccines are not available.  Cell-surface lipopolysaccharides (LPS) and capsular polysaccharides (CPS) are attractive targets for vaccine development. We present a method to synthesize LPS substructures, covering over 70% of virulent KP strains that were used to characterize the antibody repertoire of infected patients. Thereby, glycoconjugate vaccine leads against the Klebsiella pneumoniae serotypes O1, O2a, O2afg and O2ac have been identified., (© 2024 Wiley‐VCH GmbH.)

Acinetobacter baumannii is a opportunistic bacterial pathogen responsible for serious nosocomial infections that is becoming increasingly resistant against antibiotics. Capsular polysaccharides (CPS) that cover A. baumannii are a major virulence factor that play an important role in pathogenesis, are used to assign serotypes and provide the basis for vaccine development. Synthetic oligosaccharides resembling the CPS of A. baumannii 17978 were printed onto microarray slides and used to screen sera from patients infected with A. baumannii as well as a monoclonal mouse antibody (mAb C8). A synthetic oligosaccharide emerged from glycan array screening as lead for the development of a vaccine against A. baumannii 17978. Tetrasaccharide 20 is a key epitope for recognition by an antibody and is a vaccine lead., (© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Here we report the first total synthesis of several oligosaccharides resembling the capsular polysaccharide of swine pathogen S. suis serotype 18 repeating unit [→3)-d-GalNAc(α1-3)[d-Glc(β1-2)]-d-GalA4OAc(β1-3)-d-GalNAc(α1-3)-d-BacNAc4NAc(α1→] n . Access to the pentasaccharide repeating unit antigen proved to be very challenging due to the poor reactivity in the context of the trisaccharide. The challenge was overcome by the creation of a galacturonic acid in a late stage of the synthesis.

Streptococcus suis bacteria are one of the most serious health problems for pigs and an emerging zoonotic agent in humans working in the swine industry. S. suis bacteria express capsular polysaccharides (CPS) a major bacterial virulence factor that define the serotypes. Oligosaccharides resembling the CPS of S. suis serotypes 2, 3, 9, and 14 have been synthesized, glycans related to serotypes 2 and 9 were placed on glycan array surfaces to screen blood from infected pigs. Lead antigens for the development of semi-synthetic S. suis serotypes 2 and 9 glycoconjugate veterinary vaccines were identified in this way., (© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Cancer treatment with antibodies (Abs) is one of the most successful therapeutic strategies for obtaining high selectivity. In this study, α-gal-Ab conjugates were developed that dramatically increased cellular cytotoxicity by recruiting natural Abs through the interaction between α-gal and anti-gal Abs. The potency of the α-gal-Ab conjugates depended on the amount of α-gal conjugated to the antibody: the larger the amount of α-gal introduced, the higher the level of cytotoxicity observed. The conjugation of antibodies with an α-gal dendrimer allowed the introduction of large amounts of α-gal to the Ab, without loss of affinity for the target cell. The method described here will enable the re-development of Abs to improve their potency., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

New (-)-5',6-dimethoxyisolariciresinol-(3″,4″-dimethoxy)-3α-O-β-d-glucopyranoside compound was isolated from the methanol extract of the bark of Aglaia eximia (Meliaceae). The chemical structure of the new compound were elucidated on the basis of spectroscopic data including, UV, IR, HR-ESI-TOFMS, 1D-NMR, 2D-NMR and comparison with those related compounds previously reported.