Total Synthesis of the Complete Protective Antigen of <i>Vibrio cholerae</i> O139

Soliman, Sameh E.; Kòváč, Pavol

doi:10.1002/anie.201606116

Cited by 12 publications

(22 citation statements)

References 21 publications

(18 reference statements)

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“…Although the academic‐scale synthesis of the conjugation ready O‐SP yielded the desired product, events on the way suggested that the original synthetic scheme would benefit from some judicious revision. Here, the revised reaction pathway towards hexasaccharide 7 is discussed in context with the original route.…”

Section: Resultsmentioning

confidence: 99%

“…The prerequisite for such work is availability of a conjugation ready protective antigen for the disease. Synthesis of fragments of the O‐SP have been reported but it was only recently that we published our preliminary report on the first synthesis of the hexasaccharide . Here, we describe full details pertaining to the larger‐scale preparation.…”

Section: Introductionmentioning

confidence: 99%

“…Here, we describe full details pertaining to the larger‐scale preparation. Rather than trying to make the synthesis short, the revised route focuses on experimental simplicity and reliable reproducibility. The conjugation of the spacer equipped, protective antigen of Vibrio cholerae O139 to a model protein carrier, BSA, is also described.…”

Section: Introductionmentioning

confidence: 99%

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O‐Specific Polysaccharide of Vibrio cholerae O139: Improved Synthesis and Conjugation to BSA by Squaric Acid Chemistry

Pfister

Soliman

et al. 2018

Eur J Org Chem

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The sequence α‐Colp‐(1→2)‐4,6‐P‐β‐d‐Galp‐(1→3)‐[α‐Colp‐(1→4)]‐β‐d‐GlcpNAc‐(1→4)‐α‐d‐GalpA‐(1→3)‐β‐d‐QuipNAc constitutes the complete O‐specific polysaccharide (O‐antigen, O‐SP) of Vibrio cholerae O139. It was chemically synthesized in a linker‐equipped, conjugation‐ready form (7) and conjugated to a model protein carrier, bovine serum albumin. The preparation involved the synthesis of a tetrasaccharide intermediate sequence β‐d‐Galp‐(1→3)‐β‐d‐GlcpNAc‐(1→4)‐α‐d‐GalpA‐(1→3)‐β‐d‐QuipNAc→linker by coupling of two disaccharide intermediates followed by a stepwise, two single‐site colitosylations. The present synthesis is an alternative to the academic, small‐scale synthesis developed earlier where the final hexasaccharide assembly was achieved by simultaneous, two‐sites colitosylation. The approach reported herein comprises a few more synthetic steps but is experimentally less demanding, minimizes separation difficulties and is more convenient when tens of mgs of the final product is required. Syntheses of non‐phosphorylated and methyl ester analogues of 7 are also described.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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O‐Specific Polysaccharide of Vibrio cholerae O139: Improved Synthesis and Conjugation to BSA by Squaric Acid Chemistry

Pfister

Soliman

et al. 2018

Eur J Org Chem

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“…Immunological memory is a hallmark of the immune system and is necessary for the successful immunization. Assessment of the immunological memory induced by priming of the immune system by vaccination should be an important factor in evaluating candidate vaccines .…”

Section: Discussionmentioning

confidence: 99%

Immunogenicity of a Glycoconjugate from Hydrazine‐Detoxified Lipopolysaccharide of Vibrio cholerae O139

Fleischhackerová‐Slimáková

Korcová

Bystrický

2017

Scand J Immunol

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A glycoconjugate (dLPS-CBSA) from hydrazine-detoxified lipopolysaccharide (LPS) of Vibrio cholerae O139 and BSA was used for immunization of BALB/c mice. The immunogenicity (concentration of induced IgG antibodies) of the conjugate was determined by enzyme-linked immunosorbent assay. The highest level of LPS-specific IgGs was found in sera collected 2 weeks after the third immunization. Both IgM and IgG antibodies present in the anti-V. cholerae O139-specific sera showed long-lasting vibriocidal activity. The glycoconjugate also stimulated production of IL-4, IL-6, IFNγ, TNFα and IL-10. Immunization with the conjugate induced significant production of both Th1 and Th2 cytokine sets, indicating balanced Th1/Th2 immune response polarization. The quantitative analysis of total and LPS-specific IgM and IgG antibodies production by B lymphocytes (from both the spleen and the bone marrow) was performed by ELISPOT assay. From the analysis of antibodies produced directly by B lymphocytes in the bone marrow (of dLPS-CBSA immunized mice), we were able to identify the IgM-IgG switch in the antibodies produced.

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“…To avoid LPS toxicity, synthetic oligosaccharides deriving from O1 and O139 O-Ag have also been produced for conjugation to carrier proteins (Saksena et al. 2006 ; Soliman and Kovac 2016 ). While a Ogawa type hexsaccharide bound to BSA induced antibodies that were protective in a challenge assay (Chernyak et al.…”

Section: Approaches For Production Of Glycoconjugate Vaccinesmentioning

confidence: 99%

Potential targets for next generation antimicrobial glycoconjugate vaccines

Micoli¹,

Costantino

Adamo

2018

FEMS Microbiology Reviews

136

109

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Cell surface carbohydrates have been proven optimal targets for vaccine development. Conjugation of polysaccharides to a carrier protein triggers a T-cell-dependent immune response to the glycan moiety. Licensed glycoconjugate vaccines are produced by chemical conjugation of capsular polysaccharides to prevent meningitis caused by meningococcus, pneumococcus and Haemophilus influenzae type b. However, other classes of carbohydrates (O-antigens, exopolysaccharides, wall/teichoic acids) represent attractive targets for developing vaccines. Recent analysis from WHO/CHO underpins alarming concern toward antibiotic-resistant bacteria, such as the so called ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) and additional pathogens such as Clostridium difficile and Group A Streptococcus. Fungal infections are also becoming increasingly invasive for immunocompromised patients or hospitalized individuals. Other emergencies could derive from bacteria which spread during environmental calamities (Vibrio cholerae) or with potential as bioterrorism weapons (Burkholderia pseudomallei and mallei, Francisella tularensis). Vaccination could aid reducing the use of broad-spectrum antibiotics and provide protection by herd immunity also to individuals who are not vaccinated.This review analyzes structural and functional differences of the polysaccharides exposed on the surface of emerging pathogenic bacteria, combined with medical need and technological feasibility of corresponding glycoconjugate vaccines.

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Total Synthesis of the Complete Protective Antigen of Vibrio cholerae O139

Cited by 12 publications

References 21 publications

O‐Specific Polysaccharide of Vibrio cholerae O139: Improved Synthesis and Conjugation to BSA by Squaric Acid Chemistry

O‐Specific Polysaccharide of Vibrio cholerae O139: Improved Synthesis and Conjugation to BSA by Squaric Acid Chemistry

Immunogenicity of a Glycoconjugate from Hydrazine‐Detoxified Lipopolysaccharide of Vibrio cholerae O139

Potential targets for next generation antimicrobial glycoconjugate vaccines

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