Bokolo Uzoamaka Clara, Dissanayake Ravindika, Ghosh Samir, Nada Shadia, Obadawo Babatunde S, Prestwich Erin G, Wall Katherine A, Sucheck Steven J
Department of Chemistry and Biochemistry, The University of Toledo, 2801 W. Bancroft Street, Toledo, OH 43606, USA.
Department of Medicinal and Biological Chemistry, The University of Toledo, 3000 Arlington Ave., Toledo, OH 43614, USA.
Molecules. 2025 Apr 11;30(8):1720. doi: 10.3390/molecules30081720.
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 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 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.
寡糖和糖缀合物在细胞识别和信号传导等各种生物过程中发挥着重要作用，因此在过去几十年里在合成和生物学领域引起了极大关注。为推动该领域发展，我们通过一个高效的23步过程实现了多糖合成位点（Psl）胞外多糖的氨基氧基糖苷五糖亚基的合成。该五糖在还原端设计有一个氨基氧基衍生物，用于通过两步基于肟的生物共轭反应与蛋白质载体CRM197结合，表位比为1:4。共轭疫苗可产生抗Psl抗体，该抗体能够识别PAO1细菌并启动对该细菌的调理吞噬杀伤作用。此外，氨基氧基糖苷可方便地与双功能醛-生物素试剂结合，该试剂可用于疫苗接种研究中抗体滴度的定量分析。
