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Found 2 structures.
Displayed structures from 1 to 2
| -4)-b-D-ManpNAc-(1-4)-a-D-Glcp-(1-3)-a-L-Rhap-(1-P- | Show graphically |
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Structure type: polymer chemical repeating unit
Trivial name: poly(glycosyl phosphate)
Compound class: CPS
Contained glycoepitopes: IEDB_136105,IEDB_142488,IEDB_144998,IEDB_146664,IEDB_158539,IEDB_158556,IEDB_225177,IEDB_885813,IEDB_885823,IEDB_983931,SB_192
A chemical synthesis has been achieved for β-D-ManNAc-(1→4)-α-D-Glc-(1→3)-L-Rha, a trisaccharide repeating unit of the capsular polysaccharide of Streptococcus pneumoniae serotype 19A, by stepwise link-up of the suitably functionalized, constituent sugar units. A beta-selective glycosylation of trimethylsilylethyl glucoside having free 4-OH with 2-(benzoyloxyimino)-2-deoxyglycosyl bromide, followed by manno-selective hydroboration, N-acetylation, and functionalization of the anomeric center (1-OSE→1-OH→1-F), gave a key disaccharide donor, β-D-ManNAc-(1→4)-α-D-Glc-(1→F. Ensuing glycosylation of an L-rhamnosyl acceptor with the donor substrate afforded, after deblocking, the target trisaccharide in 6.5% yield over 13 steps from D-glucose.
capsular polysaccharide, glycosylation, Streptococcus pneumoniae type 19A, 2-ulose oxime, β-D-mannosaminide, hydroboration
NCBI PubMed ID: 8998845The genetic basis for the structural diversity of capsule polysaccharide (CPS) in Streptococcus pneumoniae serogroup 19 (consisting of types 19F, 19A, 19B, and 19C) has been determined for the first time. In this study, the genetic basis for the 19A and 19C serotypes is described, and the structures of all four serogroup 19 cps loci and their flanking sequences are compared. Transformation studies show that the structural difference between the 19A and 19F CPSs is likely to be a consequence of differences between their respective polysaccharide polymerase genes (cps19aI and cps19fI). The CPS of type 19C differs from that of type 19B by the addition of glucose. We have identified a single gene difference between the two cps loci (cps19cS), which is likely to encode a glucosyl transferase. The arrangement of the genes within the cps19 loci is highly conserved, with 13 genes (cps19A to -H and cps19K to -O) common to all four serogroup 19 members. These cps genes encode functions required for the synthesis of the shared trisaccharide component of the group 19 CPS repeat unit structures. Furthermore, the genetic differences between the group 19 cps loci identified are consistent with the CPS structures of the individual serotypes. Functions have been assigned to nearly all of the cps19 gene products, based on either gene complementation or similarity to other proteins with known functions, and putative biosynthetic pathways for production of all four group 19 CPSs have been proposed.
biosynthesis, genetic, Streptococcus, Streptococcus pneumoniae, capsular polysaccharide, type, serogroup
NCBI PubMed ID: 10464207A comprehensive study of the base hydrolysis of all phosphodiester bond-containing capsular polysaccharides of the 23-valent pneumococcal vaccine is described here. Capsular polysaccharides from serotypes 6B, 10A, 17F, 19A, 19F, and 20 contain a phosphodiester bond that connects the repeating units in these polysaccharides (also referred to as backbone phosphodiester bonds), and polysaccharides from serotypes 11A, 15B, 18C, and 23F contain a phosphodiester bond that links a side chain to their repeating units. Molecular weight measurements of the polysaccharides, using high performance size exclusion chromatography with tandem multiangle laser light scattering and refractive index detection, was used to evaluate the kinetics of hydrolysis. The measurement of molecular weight provides a high degree of sensitivity in the case of small extents of reaction, thus allowing reliable measurements of the kinetics over short times. Pseudo-first-order rate constants for these polysaccharides were estimated using a simple model that accounts for the polydispersity of the starting sample. It was found that the relative order of backbone phosphodiester bond instability due to base hydrolysis was 19A > 10A > 19F > 6B > 17F, 20. Degradation of side-chain phosphodiester bonds was not observed, although the high degree of sensitivity in measurements is lost in this case, due to the low contribution of the side chains to the total polysaccharide molecular weight. In comparison with literature data on pneumococcal polysaccharide 6A, 19A was found to be the more labile, and hence appears to be the most labile pneumococcal polysaccharide studied to date. The rate of hydrolysis increased at higher pH and in the presence of divalent cation, but the extent was lower than expected based on similar data on RNA. Finally, the differences in the phosphodiester bond stabilities were analyzed by considering stereochemical factors in these polysaccharides. These results also provide a framework for evaluation of molecular integrity of phosphodiester-bond-containing polysaccharides in different solution conditions. Copyright 2004 Wiley Periodicals, Inc. Biopolymers, 2004
base hydrolysis, phosphodiester bond, pneumococcal polysaccharide
NCBI PubMed ID: 15307199The in vitro binding of the macrophage mannose receptor to a range of different bacterial polysaccharides was investigated. The receptor was shown to bind to purified capsular polysaccharides from Streptococcus pneumoniae and to the lipopolysaccharides, but not capsular polysaccharides, from Klebsiella pneumoniae. Binding was Ca(2+)- dependent and inhibitable with d-mannose. A fusion protein of the mannose receptor containing carbohydrate recognition domains 4-7 and a full-length soluble form of the mannose receptor containing all domains external to the transmembrane region both displayed very similar binding specificities toward bacterial polysaccharides, suggesting that domains 4-7 are sufficient for recognition of these structures. Surprisingly, no direct correlation could be made between polysaccharide structure and binding to the mannose receptor, suggesting that polysaccharide conformation may play an important role in recognition. The full-length soluble form of the mannose receptor was able to bind simultaneously both polysaccharide via the carbohydrate recognition domains and sulfated oligosaccharide via the cysteine-rich domain. The possible involvement of the mannose receptor, either cell surface or soluble, in the innate and adaptive immune responses to bacterial polysaccharides is discussed
Lipopolysaccharide, conformation, lipopolysaccharides, oligosaccharide, structure, correlation, Bacterial, role, capsular, polysaccharide, Streptococcus, Streptococcus pneumoniae, D-mannose, capsular polysaccharide, capsular polysaccharides, polysaccharides, carbohydrate, cell, Research, form, recognition, involvement, protein, response, specificity, Klebsiella, Bacterial polysaccharide, region, external, surface, polysaccharide structure, purified, Klebsiella pneumoniae, bacterial polysaccharides, binding, domain, domains, vaccine, immune response, Mannose, immune, in vitro, macrophage, soluble, receptor, sulfated, pathology, carbohydrate recognition, carbohydrate recognition domain, fusion, fusion protein, transmembrane
NCBI PubMed ID: 12196537A method utilizing NMR spectroscopy has been developed to confirm the identity of bacterial polysaccharides used to formulate a polyvalent pneumococcal polysaccharide vaccine. The method is based on 600 MHz proton NMR spectra of individual serotype-specific polysaccharides. A portion of the anomeric region of each spectrum (5.89 to 4.64 ppm) is compared to spectra generated for designated reference samples for each polysaccharide of interest. The selected region offers a spectral window that is unique to a given polysaccharide and is sensitive to any structural alteration of the repeating units. The similarity of any two spectral profiles is evaluated using a correlation coefficient (rho), where rho >/= 0.95 between a sample and reference profile indicates a positive identification of the sample polysaccharide. This method has been shown to be extremely selective in its ability to discriminate between serotype-specific polysaccharides, some of which differ by no more than a single glycosidic linkage. Furthermore, the method is rapid and does not require extensive sample manipulations or pretreatments. The method was validated as a qualitative identity assay and will be incorporated into routine quality control testing of polysaccharide powders to be used in preparation of the polyvalent pneumococcal vaccine PNEUMOVAX 23. The specificity and reproducibility of the NMR-based identity assay is superior to the currently used colorimetric assays and can be readily adapted for use with other bacterial polysaccharide preparations as well.
NMR, Bacterial, polysaccharide, polysaccharides, Bacterial polysaccharide, bacterial polysaccharides, assay, development, identity assay, method development, validation
NCBI PubMed ID: 10706792No abstract
polysaccharide, Streptococcus, polysaccharides, Research, hydrolysis, phosphodiester, pneumococcal, PDF, P, pneumococcal polysaccharides
NCBI PubMed ID: 15761954An anomeric phosphodiester linkage formed by a glycosyl phosphate unit and a hydroxyl group of another monosaccharide is found in many glycopolymers of the outer membrane in bacteria (e.g., capsular polysaccharides and lipopolysaccharides), yeasts and protozoa. The polymers (phosphoglycans) composed of glycosyl phosphate (or oligoglycosyl phosphate) repeating units could be chemically classified as poly(glycosyl phosphates). Their importance as immunologically active components of the cell wall and/or capsule of numerous microorganisms upholds the need to develop routes for the chemical preparation of these biopolymers. In this paper, we (1) present a review of the primary structures (known to date) of natural phosphoglycans from various sources, which contain glycosyl phosphate units, and (2) discuss different approaches and recent achievements in the synthesis of glycosyl phosphosaccharides and poly(glycosyl phosphates).
synthesis, structure, polysaccharides, Phosphoglycans, Anomeric phosphodiesters
NCBI PubMed ID: 17092493The recently described [Attolino, E.; Bonaccorsi, F.; Catelani, G.; D'Andrea, F. Carbohydr. Res. 2008, 343, 2545-2556.] β-D-MaNAcp-(1→4)-β-D-Glcp thiophenyl glycosyl donor 3 was used in alpha-glycosylation reactions of OH-2 and OH-3 of the suitably protected p-MeO-benzyl α-L-rhamnopyranoside acceptors 7 and 8. Glycosylation of the axial OH-2 of 7 took place in high yield (76%) and with acceptable stereoselectivity (alpha/beta=3.4) leading to the protected trisaccharide alpha-11, corresponding to the repeating unit of Streptococcus pneumoniae 19F. The same reaction on equatorial OH-3 of acceptor 8 gave the trisaccharide alpha-15, a constituent of the repeating unit of S. pneumoniae 19A, but in lower yield (41%) and without stereoselection (alpha/beta=1:1.3). Utilizing the introduced orthogonal protection of OH-1 and OH-4'', the trisaccharide alpha-11 was transformed into a trisaccharide building block suitable for the synthesis of its phosphorylated oligomers.
Streptococcus pneumoniae, glycoconjugate vaccines, oligosaccharide synthesis, glycosylation, Thioglycosides
NCBI PubMed ID: 19467536Streptococcus pneumoniae, a major human pathogen, expresses at least 91 serologically distinct carbohydrate capsules. Since pneumococcal vaccines are designed to elicit antibodies against many different capsular polysaccharides (PSs), it is important to identify the epitopes involved in eliciting anti-capsular PS antibodies. We investigated the epitopes recognized by Dob1, which is a hybridoma-secreting human immunoglobulin G2 antibody to the PS of serotype 6B (Y. Sun et al., Infect. Immun. 67:1172-1179, 1999). We found that Dob1 bound synthetic capsular carbohydrates Gal(1→3)α-D-Glcp(1→3)α-L-Rhap(1→3)Rib-ol and α-D-Glcp(1→3)α-L-Rhap(1→3)Rib-ol but did not bind α-L-Rhap(1→3)Rib-ol. The critical epitope α-D-Glcp(1→3)α-L-Rhap is found in the capsular PSs of serotypes 6A, 6B, 6C, and 19A but not in the 19F PS. Consistent with this observation, Dob1 bound to the PSs of serotypes 6A, 6B, 6C, and 19A but did not bind the 19F PS and 23 additional unrelated pneumococcal capsular PSs. Also, Dob1 could opsonize pneumococci expressing serotypes 6A, 6B, 6C, and 19A but did not opsonize 19F pneumococci. In addition, ca. 7% of immune sera (12 of 175 sera) had significant amounts of Dob1-like antibodies, i.e., reacted with 6B and 19A PSs, but not with 19F PS. Humans can produce antibodies to the Dob1 epitope and the antibodies to that epitope cross-react with the four serotypes 6A, 6B, 6C, and 19A that belong to different serogroups. This epitope may be useful for producing a totally synthetic, simple chemical structure that is capable of generating protective antibodies to multiple pneumococcal serogroups.
Bacterial, Streptococcus pneumoniae, antibodies, Bacterial Capsule, sepitopes, Pneumococcal Infections
NCBI PubMed ID: 19451241The structural modifications and immunochemical activities of several Streptococcus pneumoniae type 19A polysaccharide (PS) preparations have been studied by sugar compositional analysis and immunodiffusion. The 19A PS preparations Lab-A-1 and Lab-A-3 and one PS isolated from 19A strain OB contained fucose (Fuc) and galactose (Gal) in addition to rhamnose (Rha) and glucose (Glc). In contrast, 19A PSs Lab-A-2 and Lab-B contained only Rha and Glc. Despite their different sugar compositions, these 19A preparations appeared to be identical in serologic activity as measured by immunodiffusion with rabbit 19A and 19F antisera. The 19A PS Lab-A-1 was separated into three fractions by DEAE-Sepharose CL-6B column chromatography with a NaCl gradient. Fraction II was the major peak with a yield of 72.9%. Fraction Ia contained Fuc and Gal, while fraction II contained Fuc, Gal, Rha, and Glc. Fractions Ia and Ib did not react with rabbit 19A antiserum. In contrast, 19A PS Lab-A-2 displayed only one peak, which was eluted by a NaCl gradient (0 to 0.6 M NaCl), and contained only Rha and Glc. The 19A PSs prepared from Lab-A and Centers for Disease Control (CDC) strains and grown in pneumococcal inoculum medium (PIM) and modified Holt medium were chromatographed on a DEAE-Sepharose CL-6B column, and the separated fractions were examined for their sugar composition. The fractions obtained from the 19A PSs Lab-A-PIM and CDC-PIM exhibited four sugar components, as observed for the PS Lab-A-1, while the separated fractions from the 19A PSs Lab-A-Holt and CDC-Holt displayed two sugar components, a pattern similar to that of PS Lab-A-2. Thus, the sugar compositions of 19A PS appeared to vary according to the type of culture medium used to grow the 19A organisms.
structure, Streptococcus pneumoniae, capsular polysaccharide, culture conditions
NCBI PubMed ID: 3610316Streptococcus pneumoniae causes meningitis, pneumonia and severe invasive disease (IPD) in young children. Although widespread infant immunisation with the PCV7 seven-valent pneumococcal conjugate vaccine has led to a dramatic decrease in IPD, infections due to non-vaccine serotypes, particularly serotype 19A, have increased. As the 19F polysaccharide differs from 19A at a single linkage position, it was assumed that PCV7 (containing 19F) would cross-protect against 19A disease. However, vaccination with PCV7 results in only 26% effectiveness against IPD caused by 19A. We explored the conformations and dynamics of the polysaccharide repeating units from serotypes 19F and 19A, comparing free energy surfaces for glycosidic linkages with 100ns aqueous molecular dynamics simulations of the di- and trisaccharide components. All calculations were performed with both the CHARMM and the GLYCAM carbohydrate force fields to establish whether the choice of model affects the predicted molecular behaviour. Although we identified key differences between the force fields, overall they were in agreement in predicting a 19F repeating unit with a wider range of conformation families than the more restricted 19A trisaccharide. This suggests a probable conformational difference between the 19F and 19A polysaccharides, which may explain the low cross-protection of 19F vaccines against 19A disease.
molecular modelling, conformation, chemistry, disease, invasive, polysaccharide, serotype, Streptococcus, Streptococcus pneumoniae, repeating unit, trisaccharide, polysaccharides, Serotypes, carbohydrate, molecular, Research, glycosidic linkage, infection, conformational, dynamics, molecular dynamics, serogroup, linkage, families, position, surface, vaccines, calculation, computer, difference, component, aqueous, vaccine, pneumococcal, simulation, conjugate, children, pneumonia, conjugate vaccine, model, decrease, free, force field, meningitis, energy, vaccination, pneumococcal conjugate vaccine, Science, cross-protection, effectiveness, Infant
Publication DOI: 10.1016/j.carres.2014.02.026Streptococcus pneumoniae is a significant pathogen in children. Although the PCV7 pneumococcal conjugate vaccine has reduced pneumococcal disease, non-vaccine serotype 19A infection has increased, despite expectations of cross-protection from vaccine serotype 19F. Serotype 19A is included in the new PCV13 vaccine, but not in PCV10. In the solution simulations of 19F and 19A oligosaccharide chains reported here, both polysaccharides form unstructured random coils, with inflexible repeat units linked by mobile phosphodiester linkages. However, there are clear conformational differences. In the 19F repeat unit, the rhamnose residue is nearly orthogonal to the other residues, whereas 19A has residues in similar orientations. This finding is corroborated by key inter-residue distances calculated from NMR NOESY experiments. Further, 19F is predominantly in extended conformations, whereas 19A exhibits a high prevalence of tight hairpin bends. These conformational differences may account for a lack of antibody cross-protection between serotypes 19F and 19A.
molecular modelling, Streptococcus pneumoniae, vaccine, pneumococcal, cross protection
NCBI PubMed ID: 25658063Streptococcus pneumoniae (the pneumococcus) is an important human pathogen. Its virulence is largely due to its polysaccharide capsule, which shields it from the host immune system, and because of this, the capsule has been extensively studied. Studies of the capsule led to the identification of DNA as the genetic material, identification of many different capsular serotypes, and identification of the serotype-specific nature of protection by adaptive immunity. Recent studies have led to the determination of capsular polysaccharide structures for many serotypes using advanced analytical technologies, complete elucidation of genetic basis for the capsular types, and the development of highly effective pneumococcal conjugate vaccines. Conjugate vaccine use has altered the serotype distribution by either serotype replacement or switching, and this has increased the need to serotype pneumococci. Due to great advances in molecular technologies and our understanding of the pneumococcal genome, molecular approaches have become powerful tools to predict pneumococcal serotypes. In addition, more-precise and -efficient serotyping methods that directly detect polysaccharide structures are emerging. These improvements in our capabilities will greatly enhance future investigations of pneumococcal epidemiology and diseases and the biology of colonization and innate immunity to pneumococcal capsules.
serotype, Streptococcus pneumoniae, vaccines, Pneumococcal Capsules
NCBI PubMed ID: 26085553Physicochemical techniques are a powerful tool for the structural characterization of carbohydrate-based vaccines. High-field Nuclear Magnetic Resonance (NMR) spectroscopy has been established as an extremely useful and robust method for tracking the industrial manufacturing process of these vaccines from polysaccharide bulk antigen through to the final formulation. Here, we describe the use of proton NMR for structural identity and conformity testing of carbohydrate-based vaccines.
carbohydrates, capsular polysaccharide, antigens, nuclear magnetic resonance spectroscopy, vaccines
NCBI PubMed ID: 26169742Streptococcus suis serotypes 7 and 8 are counted among the top six S. suis serotypes causing clinical disease in pigs. Yet, limited information is available on these serotypes. Since S. suis serotyping system is based upon capsular polysaccharide (CPS) antigenicity and the CPS is considered a major virulence factor for encapsulated pathogens, here we determined for the first time the chemical compositions and structures of serotypes 7 and 8 CPSs. Chemical and spectroscopic data gave the following repeating unit sequences: [3)L-Rha(α1-P-2)D-Gal(α1-4)D-GlcA(β1-3)D-FucNAc4N(α1-]n for serotype 7 and [2)L-Rha(α1-P-4)D-ManNAc(β1-4)D-Glc(α1-]n for serotype 8. As serotype 8 CPS is identical to Streptococcus pneumoniae type 19F CPS, dot-blot analyses showed a strong reaction of the 19F polysaccharide with reference anti-S. suis serotype 8 rabbit serum. A correlation between S. suis serotypes 7 and 8 sequences and genes of those serotypes' loci encoding putative glycosyltransferases and polymerases responsible for the biosynthesis of the repeating units was tentatively established. Knowledge of CPS structure and composition will contribute to better dissect the role of this bacterial component in the pathogenesis of the disease caused by S. suis serotypes 7 and 8.
capsular polysaccharide, carbohydrate structure, Serotype 8, Streptococcus suis, Serotype 7
NCBI PubMed ID: 30605786Pneumococcal cell wall polysaccharide (C-PS), a contaminant in pneumococcal capsular polysaccharide (Pn-PS) vaccines is degraded by mild deamination of the 4-amino-2-acetamido-2,4,6-tri-deoxy-galactose (AAT) in C-PS, which was carried out by addition of 5% aqueous sodium nitrite to a solution of polysaccharide in 5% aqueous acetic acid. Glycosidic linkage and functional groups such as O-acetates, phosphodiesters, and pyruvates were preserved under the conditions. The small fragments from degraded C-PS were removed by ultrafiltration or dialysis to provide essentially C-PS free Pn-PS. Because of the presence of AAT in its structure the deamination is not suitable for the purification of type 1 Pn-PS. Meanwhile, the mass and NMR spectroscopic analysis on the deamination products suggests that both type 1 Pn-PS and C-PS degraded following a major pathway of 5,4-hydride shift, cleavage of AAT O5-C1 bond, C1 hemiacetal formation, and its hydrolysis to release neighboring GalA- in type 1 Pn-PS and GalNAc(6-O-PCho)- in C-PS
mechanism, degradation, deamination, cell wall polysaccharide, pneumococcal capsular polysaccharide
NCBI PubMed ID: 31221321Bacterial extracellular polysaccharides are known as a cell-bound capsule, a sheath, or a slime, which is excreted into the environment. They play an important role in virulence of medical bacteria and plant-to-symbiont interaction and are used for serotyping of bacteria and production of vaccines. Some exopolysaccharides have commercial applications in industry, and claims of health benefits have been documented for an increasing number of them. Exopolysaccharides have diverse composition and structure, and some contain sugar and non-sugar components that are found in bacterial carbohydrates only. The present article provides an updated collection of the data on exopolysaccharides of various classes of gram-negative and gram-positive bacteria reported until the end of 2019. When known, biosynthesis pathways of exopolysaccharides are treated in a summary manner. References are made to structure and biosynthesis relatedness between exopolysaccharides of different bacterial taxa as well as between bacterial polysaccharides and mammalian glycosaminoglycans.
polysaccharide structure, Gram-negative bacteria, capsule, Biofilm, polysaccharide biosynthesis, gram-positive bacteria, Monosaccharide composition, Bacterial exopolysaccharide, non-sugar component
Publication DOI: 10.1016/B978-0-12-819475-1.00005-5The polysaccharide capsule of Streptococcus pneumoniae constitutes the outermost surface structure of the organism and plays a critical role in virulence. The capsule is the target of current pneumococcal vaccines and glycoconjugates and has important medical and industrial applications. Widespread use of these vaccines is driving changes in serotype prevalence in disease. A massive array of sugars and glycosidic linkages experienced with complete diversity of potential polysaccharide structures. However, it is impossible to collect a sufficient quantity of glycan antigens for the preparation of CPS-based glycoconjugate vaccines from natural sources with high purity and for thorough biological evaluation. So nowadays, the development of a chemical synthetic strategy and their conjugation with a carrier protein to form synthetic glycoconjugate vaccines has been used to gain access on a large scale. This review provides a comprehensive summary of structures, synthesis as well as recent development of synthetic glycoconjugate vaccines, which will support research and may benefit the glycochemical and medical sciences.
synthesis, Streptococcus pneumoniae, polysaccharides, glycoconjugate vaccines, Pneumococcal Infections
NCBI PubMed ID: 33743443Vaccination represents the most effective way to prevent invasive pneumococcal diseases. The glycoconjugate vaccines licensed so far are obtained from capsular polysaccharides (CPSs) of the most virulent serotypes. Protection is largely limited to the specific vaccine serotypes, and the continuous need for broader coverage to control the outbreak of emerging serotypes is pushing the development of new vaccine candidates. Indeed, the development of efficacious vaccine formulation is complicated by the high number of bacterial serotypes with different CPSs. In this context, to simplify vaccine composition, we propose the design of new saccharide fragments containing chemical structures shared by different serotypes as cross-reactive and potentially cross-protective common antigens. In particular, we focused on Streptococcus pneumoniae (Sp) 19A and 19F. The CPS repeating units of Sp 19F and 19A are very similar and share a common structure, the disaccharide ManNAc-β-(1→4)-Glc (A-B). Herein, we describe the synthesis of a small library of compounds containing different combinations of the common 19F/19A disaccharide. The six new compounds were tested with a glycan array to evaluate their recognition by antibodies in reference group 19 antisera and factor reference antisera (reacting against 19F or 19A). The disaccharide A-B, phosphorylated at the upstream end, emerged as a hit from the glycan array screening because it is strongly recognized by the group 19 antisera and by the 19F and 19A factor antisera, with similar intensity compared with the CPSs used as controls. Our data give a strong indication that the phosphorylated disaccharide A-B can be considered a common epitope among different Sp 19 serotypes.
Streptococcus pneumoniae, capsular polysaccharides, glycan, disaccharide, glycoconjugate vaccine, vaccination, glycan epitopes
NCBI PubMed ID: 34469105Polysaccharide (Ps) activation evaluation is an imperative quality attribute in a conjugate vaccine. Pneumococcal polysaccharide (PnPs) serotypes 5, 6B, 14, 19A and 23F were cyanylated for 3 and 8 min. The cyanylated and non-cyanylated polysaccharides were methanolysed and derivatized to assess the activation of each sugar by GC-MS. The activation of 22 and 27% serotype 6B and 11 and 36% in serotype 23 F Ps at 3 and 8 min respectively showed controlled conjugation kinetics with CRM197 carrier protein estimated by SEC-HPLC and optimal absolute molar mass by SEC-MALS. The Glc and Gal are the most commonly activated sugars of all PnPs serotypes while N-acetyl sugars PneuNAc, GalNAc and Rha in serotypes 5, 14 and 19A respectively showed >50% activation which contributes to conjugate aggregate formation at 8 min compared to 3 min cyanylation. The GC-MS analysis of structural modifications at functional groups entails important information to characterize the activated polysaccharide for consistent conjugate vaccine manufacturing.
activation, conjugate vaccine, pneumococcal polysaccharide, GC-MS, cyanylation, SEC-HPLC, SEC-MALS
NCBI PubMed ID: 37390792| -3)-a-L-Rhap-(1--P--4)--b-D-ManpNAc-(1-4)-a-D-Glcp-(1- | Show graphically |
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Structure type: polymer biological repeating unit
Compound class: CPS
Contained glycoepitopes: IEDB_136105,IEDB_142488,IEDB_144998,IEDB_146664,IEDB_158539,IEDB_158556,IEDB_225177,IEDB_885813,IEDB_885823,IEDB_983931,SB_192
The polysaccharide capsule of Streptococcus pneumoniae is the dominant surface structure of the organism and plays a critical role in virulence, principally by interfering with host opsonophagocytic clearance mechanisms. The capsule is the target of current pneumococcal vaccines, but there are 98 currently recognised polysaccharide serotypes and protection is strictly serotype-specific. Widespread use of these vaccines is driving changes in serotype prevalence in both carriage and disease. This chapter summarises current knowledge on the role of the capsule and its regulation in pathogenesis, the mechanisms of capsule synthesis, the genetic basis for serotype differences, and provides insights into how so many structurally distinct capsular serotypes have evolved. Such knowledge will inform ongoing refinement of pneumococcal vaccination strategies.
Streptococcus pneumoniae, capsular polysaccharide, gene cluster, function analysis, pneumococcal vaccines
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