Chemical Synthesis and Antigenic Evaluation of Inner Core Oligosaccharides from Acinetobacter baumannii Lipopolysaccharide

Abstract

Acinetobacter baumannii is currently posing a serious threat to global health. Lipopolysaccharide (LPS) is a potent virulence factor of pathogenic Gram-negative bacteria. To explore the antigenic properties of A. baumannii LPS, four Kdo-containing inner core glycans from A. baumannii strain ATCC 17904 were synthesized. A flexible and divergent method based on the use of the orthogonally substituted α-Kdo-(2!5)-Kdo disaccharides was developed. Selective removal of different protecting groups in these key precursors and elongation of sugar chain via αstereocontrolled coupling with 5,7-O-di-tert-butylsilylene or 5-O-benzoyl protected Kdo thioglycosides and 2-azido-2deoxyglucosyl thioglycoside allowed efficient assembly of the target molecules. Glycan microarray analysis of sera from infected patients revealed that the 4,5-branched Kdo trimer was a potential antigenic epitope, which is attractive for further immunological research to develop carbohydrate vaccines against A. baumannii.

ortho-Methoxycarbonylethynylphenyl Thioglycosides (MCEPTs): Versatile Glycosyl Donors Enabled by Electron-Withdrawing Substituents and Catalyzed by Gold(I) or Cu(II) Complexes

“…As surface polysaccharides including lipopolysaccharides (LPSs) and capsular polysaccharides (CPSs) play essential roles in the pathogenesis of Gram-negative bacteria, investigations aimed at the development of surface polysaccharide-based carbohydrate vaccines against A. baumannii have been extensively launched. 46 However, low efficiency in access to structurally defined surface polysaccharide derivatives of A. baumannii seriously retards the progress of sugar-based vaccine development. Meanwhile, the surface polysaccharides of A. baumannii constitute an ideal testing ground for the newly devised MCEPT glycosylation protocol.…”

“…As surface polysaccharides including lipopolysaccharides (LPSs) and capsular polysaccharides (CPSs) play essential roles in the pathogenesis of Gram-negative bacteria, investigations aimed at the development of surface polysaccharide-based carbohydrate vaccines against A. baumannii have been extensively launched . However, low efficiency in access to structurally defined surface polysaccharide derivatives of A.…”

Chemical Synthesis of the Nonreducing Hexasaccharide Fragment of Axinelloside A Based on a Stepwise Glycosylation Approach

“…As determined by the small J H1″,H2″ coupling value (3.4 Hz) in the 1 H NMR spectrum of 16 , complete β-selectivity was achieved in this glycosylation reaction. The anomeric allyl ether of 16 was cleaved by isomerization in the presence of [Ir­(COD)­(CH 3 Ph 2 P) 2 ]­PF 6 followed by hydrolysis using HgO/HgCl 2 , giving rise to a hemiacetal intermediate that was then converted into the corresponding N -phenyltrifluoroacetimidate 4 by treatment with CF 3 C­(NPh)Cl in the presence of DMAP/DIPEA.…”

Total Synthesis of Conjugation-Ready Tetrasaccharide Repeating Units of a Multidrug-Resistant Pathogen Acinetobacter baumannii Strain 34 and O5

“…For this purpose, chemically pure and structurally well characterized synthetic epitopes with a functionalized linker for protein attachment are required. There are a few reports in literature on chemical synthesis of other Acinetobacter baumannii strains. − Herein, we report the first total synthesis of conjugation-ready tetrasaccharide repeating units of Acinetobacter baumannii strain 34 ( 1a ) and O5 ( 1b ) (Scheme ).…”