Synthesis of the Pentasaccharide Unit of the <i>Pseudomonas aeruginosa</i> Exopolysaccharide Psl Conjugation with CRM197, and Evaluation of Antigenicity in a QS-21/Pam<sub>3</sub>CSK<sub>4</sub>-Liposomal Formulation
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 s...
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2025-04-01
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| author | Uzoamaka Clara Bokolo Ravindika Dissanayake Samir Ghosh Shadia Nada Babatunde S. Obadawo Erin G. Prestwich Katherine A. Wall Steven J. Sucheck |
| author_facet | Uzoamaka Clara Bokolo Ravindika Dissanayake Samir Ghosh Shadia Nada Babatunde S. Obadawo Erin G. Prestwich Katherine A. Wall Steven J. Sucheck |
| author_sort | Uzoamaka Clara Bokolo |
| collection | DOAJ |
| description | 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 <i>Pseudomonas aeruginosa</i> 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 <i>P. aeruginosa</i> 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. |
| format | Article |
| id | doaj-art-366fda24559c415b8a2230f6c80c0d92 |
| institution | OA Journals |
| issn | 1420-3049 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | MDPI AG |
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| series | Molecules |
| spelling | doaj-art-366fda24559c415b8a2230f6c80c0d922025-08-20T02:28:19ZengMDPI AGMolecules1420-30492025-04-01308172010.3390/molecules30081720Synthesis of the Pentasaccharide Unit of the <i>Pseudomonas aeruginosa</i> Exopolysaccharide Psl Conjugation with CRM197, and Evaluation of Antigenicity in a QS-21/Pam<sub>3</sub>CSK<sub>4</sub>-Liposomal FormulationUzoamaka Clara Bokolo0Ravindika Dissanayake1Samir Ghosh2Shadia Nada3Babatunde S. Obadawo4Erin G. Prestwich5Katherine A. Wall6Steven J. Sucheck7Department of Chemistry and Biochemistry, The University of Toledo, 2801 W. Bancroft Street, Toledo, OH 43606, USADepartment of Medicinal and Biological Chemistry, The University of Toledo, 3000 Arlington Ave., Toledo, OH 43614, USADepartment of Chemistry and Biochemistry, The University of Toledo, 2801 W. Bancroft Street, Toledo, OH 43606, USADepartment of Medicinal and Biological Chemistry, The University of Toledo, 3000 Arlington Ave., Toledo, OH 43614, USADepartment of Chemistry and Biochemistry, The University of Toledo, 2801 W. Bancroft Street, Toledo, OH 43606, USADepartment of Medicinal and Biological Chemistry, The University of Toledo, 3000 Arlington Ave., Toledo, OH 43614, USADepartment of Medicinal and Biological Chemistry, The University of Toledo, 3000 Arlington Ave., Toledo, OH 43614, USADepartment of Chemistry and Biochemistry, The University of Toledo, 2801 W. Bancroft Street, Toledo, OH 43606, USAOligosaccharides 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 <i>Pseudomonas aeruginosa</i> 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 <i>P. aeruginosa</i> 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.https://www.mdpi.com/1420-3049/30/8/1720<i>Pseudomonas aeruginosa</i>Psl exopolysaccharidecarbohydrate vaccineβ-mannosideCRM197QS21 |
| spellingShingle | Uzoamaka Clara Bokolo Ravindika Dissanayake Samir Ghosh Shadia Nada Babatunde S. Obadawo Erin G. Prestwich Katherine A. Wall Steven J. Sucheck Synthesis of the Pentasaccharide Unit of the <i>Pseudomonas aeruginosa</i> Exopolysaccharide Psl Conjugation with CRM197, and Evaluation of Antigenicity in a QS-21/Pam<sub>3</sub>CSK<sub>4</sub>-Liposomal Formulation Molecules <i>Pseudomonas aeruginosa</i> Psl exopolysaccharide carbohydrate vaccine β-mannoside CRM197 QS21 |
| title | Synthesis of the Pentasaccharide Unit of the <i>Pseudomonas aeruginosa</i> Exopolysaccharide Psl Conjugation with CRM197, and Evaluation of Antigenicity in a QS-21/Pam<sub>3</sub>CSK<sub>4</sub>-Liposomal Formulation |
| title_full | Synthesis of the Pentasaccharide Unit of the <i>Pseudomonas aeruginosa</i> Exopolysaccharide Psl Conjugation with CRM197, and Evaluation of Antigenicity in a QS-21/Pam<sub>3</sub>CSK<sub>4</sub>-Liposomal Formulation |
| title_fullStr | Synthesis of the Pentasaccharide Unit of the <i>Pseudomonas aeruginosa</i> Exopolysaccharide Psl Conjugation with CRM197, and Evaluation of Antigenicity in a QS-21/Pam<sub>3</sub>CSK<sub>4</sub>-Liposomal Formulation |
| title_full_unstemmed | Synthesis of the Pentasaccharide Unit of the <i>Pseudomonas aeruginosa</i> Exopolysaccharide Psl Conjugation with CRM197, and Evaluation of Antigenicity in a QS-21/Pam<sub>3</sub>CSK<sub>4</sub>-Liposomal Formulation |
| title_short | Synthesis of the Pentasaccharide Unit of the <i>Pseudomonas aeruginosa</i> Exopolysaccharide Psl Conjugation with CRM197, and Evaluation of Antigenicity in a QS-21/Pam<sub>3</sub>CSK<sub>4</sub>-Liposomal Formulation |
| title_sort | synthesis of the pentasaccharide unit of the i pseudomonas aeruginosa i exopolysaccharide psl conjugation with crm197 and evaluation of antigenicity in a qs 21 pam sub 3 sub csk sub 4 sub liposomal formulation |
| topic | <i>Pseudomonas aeruginosa</i> Psl exopolysaccharide carbohydrate vaccine β-mannoside CRM197 QS21 |
| url | https://www.mdpi.com/1420-3049/30/8/1720 |
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