Synthesis of the Pentasaccharide Unit of the Pseudomonas aeruginosa Exopolysaccharide Psl Conjugation with CRM197, and Evaluation of Antigenicity in a QS-21/Pam3CSK4-Liposomal Formulation
2025
Uzoamaka Clara Bokolo | Ravindika Dissanayake | Samir Ghosh | Shadia Nada | Babatunde S. Obadawo | Erin G. Prestwich | Katherine A. Wall | Steven J. Sucheck
Oligosaccharides and glycoconjugates play essential roles in various biological processes such as cellular recognition and signaling, and thus have attracted tremendous attention in the synthetic and biological communities over the past few decades. Contributing to this field, we have achieved the synthesis of the aminoxyglycoside pentasaccharide subunit of Pseudomonas aeruginosa polysaccharide synthesis locus (Psl) exopolysaccharide through an efficient 23 step process. This pentasaccharide was designed with an aminooxy derivative at the reducing end, which was used in a 2-step oxime-based bioconjugation to the protein carrier CRM197, with an epitope ratio of 1:4. The conjugate vaccine could generate anti-Psl antibodies that could recognize P. aeruginosa PAO1 bacteria and initiate opsonophagocytic killing of the bacteria. In addition, the aminoxyglycoside could be conveniently conjugated to a bifunctional aldehyde-biotin reagent, which can be used for quantifying antibody titers in vaccination studies.
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