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1.
Carbohydr Res ; 511: 108476, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34800752

ABSTRACT

A linear tetramer of ß-(1 â†’ 6)-linked 3-azido-3-deoxy-d-allose containing glycosyl donor and glycosyl acceptor functions in the terminal monosaccharide units was prepared starting from 3-azido-3-deoxy-1,2:5,6-di-O-isopropylidene-α-d-allofuranose. Cyclization of the linear tetramer under glycosylation conditions afforded the corresponding cyclic tetrasaccharide in 77% yield; its deprotection and reduction of the azido groups resulted in the formation of the cyclic tetramer of 3-amino-3-deoxy-d-allose with axial amino groups, a potential scaffold for the synthesis of tetravalent functional clusters.


Subject(s)
Oligosaccharides , Glycosylation
2.
Int J Mol Sci ; 21(21)2020 Nov 05.
Article in English | MEDLINE | ID: mdl-33167433

ABSTRACT

High-resolution electrospray mass spectra (MS and MS/MS CID) of positive ions of a series of protonated, ammoniated, and metallated molecules of cyclic N-substituted oligo-ß-(1→6)-D-glucosamines differing in cycle size and N-acyl substituents were registered and interpreted. It was shown that the main type of fragmentation is a cleavage of glycosidic bonds of a cycle, and in some cases fragmentation of amide side chains is possible. If labile fragments in substituents (e.g., carbohydrate chains) are present, a decay of the cycle and an elimination of labile fragments are of comparable possibility. It was found that in some cases rearrangements with loss of an internal carbohydrate residue (IRL), or an internal part of a side chain, are feasible.


Subject(s)
Glucosamine/analogs & derivatives , Glucosamine/chemistry , Oligosaccharides/chemistry , Spectrometry, Mass, Electrospray Ionization/methods , Tandem Mass Spectrometry/methods , Cyclization
3.
Drug Discov Today Technol ; 35-36: 13-21, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33388124

ABSTRACT

Poly-ß-(1→6)-N-acetylglucosamine (PNAG) was first discovered as a major component of biofilms formed by Staphylococcus aureus and some other staphylococci but later this exopolysaccharide was also found to be produced by pathogens of various nature. This common antigen is considered as a promising target for construction of a broadly protective vaccine. Extensive studies of PNAG, its de-N-acetylated derivative (dPNAG, containing around 15% of residual N-acetates) and their conjugates with Tetanus Toxoid (TT) revealed the crucial role of de-N-acetylated glucosamine units for the induction of protective immunity. Conjugates of synthetic penta- (5GlcNH2) and nona-ß-(1→6)-d-glucosamines (9GlcNH2) were tested in vitro and in different animal models and proved to be effective in passive and active protection against different microbial pathogens. Presently conjugate 5GlcNH2-TT is being produced under GMP conditions and undergoes safety and effectiveness evaluation in humans and economically important animals. Current review summarizes all stages of this long-termed study.


Subject(s)
Bacterial Infections/prevention & control , Bacterial Vaccines/administration & dosage , Polysaccharides, Bacterial/immunology , Tetanus Toxoid/administration & dosage , beta-Glucans/administration & dosage , Animals , Bacterial Infections/immunology , Bacterial Infections/microbiology , Bacterial Vaccines/chemical synthesis , Bacterial Vaccines/immunology , Disease Models, Animal , Glycoconjugates/administration & dosage , Glycoconjugates/chemical synthesis , Glycoconjugates/immunology , Humans , Immunogenicity, Vaccine , Polysaccharides, Bacterial/administration & dosage , Polysaccharides, Bacterial/chemical synthesis , Tetanus Toxoid/chemical synthesis , Tetanus Toxoid/immunology , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/chemistry , Vaccines, Synthetic/immunology , beta-Glucans/chemical synthesis , beta-Glucans/immunology
4.
Front Immunol ; 8: 659, 2017.
Article in English | MEDLINE | ID: mdl-28626461

ABSTRACT

Identifying protective synthetic oligosaccharide (OS) epitopes of Streptococcus pneumoniae capsular polysaccharides (CPs) is an indispensable step in the development of third-generation carbohydrate pneumococcal vaccines. Synthetic tetra-, hexa-, and octasaccharide structurally related to CP of S. pneumoniae type 14 were coupled to bovine serum albumin (BSA), adjuvanted with aluminum hydroxide, and tested for their immunogenicity in mice upon intraperitoneal prime-boost immunizations. Injections of the conjugates induced production of opsonizing anti-OS IgG1 antibodies (Abs). Immunization with the tetra- and octasaccharide conjugates stimulated the highest titers of the specific Abs. Further, the tetrasaccharide ligand demonstrated the highest ability to bind OS and CP Abs. Murine immune sera developed against tetra- and octasaccharide conjugates promoted pathogen opsonization to a higher degree than antisera against conjugated hexasaccharide. For the first time, the protective activities of these glycoconjugates were demonstrated in mouse model of generalized pneumococcal infections. The tetrasaccharide conjugate possessed the highest protective activities. Conversely, the octasaccharide conjugate had lower protective activities and the lowest one showed the hexasaccharide conjugate. Sera against all of the glycoconjugates passively protected naive mice from pneumococcal infections. Given that the BSA-tetrasaccharide induced the most abundant yield of specific Abs and the best protective activity, this OS may be regarded as the most promising candidate for the development of conjugated vaccines against S. pneumoniae type 14 infections.

5.
Front Immunol ; 7: 248, 2016.
Article in English | MEDLINE | ID: mdl-27446078

ABSTRACT

We report the effect of a bovine serum albumin (BSA) conjugate of a synthetic hexasaccharide (HS) related to the fragment of the capsular polysaccharide (PS) of Streptococcus pneumoniae type 14 on the stimulation of innate immune system and the subsequent development of a PS-specific antibody response. Glycoconjugate (GC) in the presence (GC + AL) or absence of aluminum hydroxide was administered to mice twice. GC increased the number of TLR2-expressing cells and induced the maturation of dendritic cells (CD11c(+), CD80(+) and, MHCII(+)), which secreted IL-1ß, IL-6, and TNFα into the culture medium. The level of IL-1ß, IL-10, IFNγ, and TNFα in the blood increased within 24 h after the single GC administration to mice. On day 7, the numbers of splenic CD4(+) and CD8(+) T lymphocytes and B lymphocytes increased. After the second immunization, the levels of CD4(+) and CD8(+) T lymphocytes were lower than in the control, whereas the B cell, NK cell, and MHC class II-expressing cell numbers remained enhanced. However, of the presence of anti-PS, IgG antibodies were not detected. The addition of aluminum hydroxide to GC stimulated the production of GM-CSF, IL-1ß, IL-5, IL-6, IL-10, IL-17, IFNγ, and TNFα. Anti-PS IgG1 antibody titers 7 days after the second immunization were high. During that period, normal levels of splenic CD4(+) T lymphocytes were maintained, whereas reduced CD8(+) T lymphocyte numbers and increased levels of B lymphocytes, NK cells, and MHC class II-expressing cell numbers were observed. Anti-PS IgG levels diminished until day 92. A booster immunization with GC + AL stimulated the production of anti-PS IgG memory antibodies, which were determined within 97 days. The elucidation of specific features of the effect of the synthetic HS conjugate on the stimulation of innate, cell-mediated immunity, and antibody response can favor the optimization of GC vaccine design.

6.
Chemistry ; 21(48): 17445-52, 2015 Nov 23.
Article in English | MEDLINE | ID: mdl-26448281

ABSTRACT

Cyclo-oligo-(1→6)-ß-D-glucosamines functionalized with hydrophobic tails are reported as a new class of transmembrane ion-transport system. These macrocycles with hydrophilic cavities were introduced as an alternative to cyclodextrins, which are supramolecular systems with hydrophobic cavities. The transport activities of these glycoconjugates were manipulated by altering the oligomericity of the macrocycles, as well as the length and number of attached tails. Hydrophobic tails of 3 different sizes were synthesized and coupled with each glucosamine scaffold through the amide linkage to obtain 18 derivatives. The ion-transport activity increased from di- to tetrameric glucosamine macrocycles, but decreased further when flexible pentameric glucosamine was introduced. The ion-transport activity also increased with increasing length of attached linkers. For a fixed length of linkers, the transport activity decreased when the number of such tails was reduced. All glycoconjugates displayed a uniform anion-selectivity sequence: Cl(-) >Br(-) >I(-) . From theoretical studies, hydrogen bonding between the macrocycle backbone and the anion bridged through water molecules was observed.


Subject(s)
Glucosamine/chemistry , Ion Transport , Adenine Nucleotides , Anions/chemistry , Glucosamine/analogs & derivatives , Hydrogen Bonding , Hydrophobic and Hydrophilic Interactions , Oligonucleotides , Oligoribonucleotides
7.
Carbohydr Res ; 417: 15-8, 2015 Nov 19.
Article in English | MEDLINE | ID: mdl-26382082

ABSTRACT

High-resolution electrospray mass spectra in positive and negative ion modes (MS and MS/MS) were measured and described for biotinylated hexaethylene glycol (HEG) connected molecular probes bearing HNK-1 (abbreviation of human natural killer cell-1 epitope) antigenic trisaccharide (1) and its non-sulfated analogue (2). For molecular probe 2, in its CID MS/MS of [M+2Na](2+), unexpected peak at m/z 530.2475 [C22H41N3O8SNa](+) was observed and attributed to the fragmentation of the aglycone at the end of the HEG chain distant from the biotin fragment. No homologous ions having the difference C2H4O smaller than that one were observed. The same cleavage was revealed in negative ion spectra. A similar fragmentation was found for other non-sulfated, biotinylated HEG-spacered molecular probes thus demonstrates this type of fragmentation characteristic for such glycosides.


Subject(s)
CD57 Antigens/chemistry , Ethylene Glycols/chemistry , Molecular Probes/chemistry , Trisaccharides/chemistry , Biotinylation , Carbohydrate Sequence , Humans , Killer Cells, Natural/chemistry , Killer Cells, Natural/immunology , Molecular Sequence Data , Spectrometry, Mass, Electrospray Ionization
8.
Chem Commun (Camb) ; 50(41): 5514-6, 2014 May 28.
Article in English | MEDLINE | ID: mdl-24710000

ABSTRACT

Unimolecular ion channels were designed by functionalization of a new type of cyclic oligosaccharides, cyclo-oligo-(1 → 6)-ß-d-glucosamines, with pentabutylene glycol chains. Their ion transporting activity was tuned by varying oligomericity. A halide selectivity sequence, Cl(-) > Br(-) > I(-) was observed.


Subject(s)
Biomimetic Materials/chemistry , Cell Membrane/metabolism , Glucosamine/chemistry , Oligosaccharides/chemistry , Carbohydrate Conformation , Ion Transport , Molecular Dynamics Simulation
9.
mBio ; 5(2): e00974-14, 2014 Mar 25.
Article in English | MEDLINE | ID: mdl-24667709

ABSTRACT

Many pathogens produce the ß-(1-6)-linked poly-N-acetylglucosamine (PNAG) surface polysaccharide that is being developed as a broadly protective antimicrobial vaccine. However, it is unknown whether systemically injected PNAG vaccines or antibodies would provide protective immunity against pathogens confined to the gastrointestinal tract such as Shiga toxin (Stx)-producing Escherichia coli (STEC), an important group of gastrointestinal (GI) pathogens for which effective immunotherapeutics are lacking. To ascertain whether systemic IgG antibody to PNAG impacts this infectious situation, a vaccine consisting of a synthetic nonamer of nonacetylated PNAG, 9GlcNH2, conjugated to the Shiga toxin 1b subunit (9GlcNH2-Stx1b) was produced. Rabbit antibodies raised to the conjugate vaccine were tested for bacterial killing and toxin neutralization in vitro and protection against infection in infant mice. Cell surface PNAG was detected on all 9 STEC isolates tested, representing 6 STEC serogroups, including E. coli O157:H7. Antibody to the 9GlcNH2-Stx1b conjugate neutralized Stx1 potently and Stx2 modestly. For O157:H7 and O104:H4 STEC strains, antibodies elicited by the 9GlcNH2-Stx1b conjugate possessed opsonic killing and bactericidal activity. Following intraperitoneal injection, antibodies to both PNAG and Stx were needed for infant mouse protection against O157 STEC. These antibodies also mediated protection against the Stx2-producing O104:H4 strain that was the cause of a recent outbreak in Germany, although sufficient doses of antibody to PNAG alone were protective against this strain in infant mice. Our observations suggest that vaccination against both PNAG and Stx, using a construct such as the 9GlcNH2-Stx1b conjugate vaccine, would be protective against a broad range of STEC serogroups. IMPORTANCE The presence of poly-N-acetylglucosamine (PNAG) on many pathogens presents an opportunity to target this one structure with a multispecies vaccine. Whether antibodies to PNAG can protect against pathogens confined to the gastrointestinal tract is not known. As Shiga toxin (Stx)-producing Escherichia coli (STEC) bacteria are serious causes of infection whose virulence is dependent on elaboration of Stx, we prepared a vaccine containing a synthetic nonamer of PNAG (9GlcNH2) conjugated to Shiga toxin 1b subunit (9GlcNH2-Stx1b) to evaluate bacterial killing, toxin neutralization, and protective efficacy in infant mice. All nine (100%) clinical strains of STEC from different serogroups expressed PNAG. Vaccine-induced antibody mediated in vitro killing of STEC and neutralization of both Stx1 and Stx2. Passive administration of antibody to the conjugate showed protection requiring immunity to both PNAG and Stx for O157 strains, although for an O104 strain, antibody to PNAG alone was protective. Immunity to PNAG may contribute to protection against STEC infections.


Subject(s)
Escherichia coli Infections/prevention & control , Escherichia coli Vaccines/immunology , Shiga Toxin/immunology , Shiga-Toxigenic Escherichia coli/immunology , beta-Glucans/immunology , Animals , Animals, Newborn , Antibodies, Bacterial/blood , Antibodies, Neutralizing/blood , Antitoxins/blood , Disease Models, Animal , Escherichia coli Infections/immunology , Escherichia coli Vaccines/administration & dosage , Mice , Microbial Viability/immunology , Opsonin Proteins/blood , Rabbits , Vaccines, Conjugate/administration & dosage , Vaccines, Conjugate/immunology
10.
Chemistry ; 19(28): 9272-85, 2013 Jul 08.
Article in English | MEDLINE | ID: mdl-23761096

ABSTRACT

A family of fifteen glycoclusters based on a cyclic oligo-(1→6)-ß-D-glucosamine core has been designed as potential inhibitors of the bacterial lectin LecA with various valencies (from 2 to 4) and linkers. Evaluation of their binding properties towards LecA has been performed by a combination of hemagglutination inhibition assays (HIA), enzyme-linked lectin assays (ELLA), and isothermal titration microcalorimetry (ITC). Divalent ligands displayed dissociation constants in the sub-micromolar range and tetravalent ligands displayed low nanomolar affinities for this lectin. The influence of the linker could also be demonstrated; aromatic moieties are the best scaffolds for binding to the lectin. The affinities observed in vitro were then correlated with molecular models to rationalize the possible binding modes of these glycoclusters with the bacterial lectin.


Subject(s)
Adhesins, Bacterial/chemistry , Glucosamine/analogs & derivatives , Glucosamine/chemistry , Glycoconjugates/chemical synthesis , Pseudomonas aeruginosa/chemistry , Glycoconjugates/chemistry , Humans , Ligands , Models, Molecular , Protein Binding
11.
Proc Natl Acad Sci U S A ; 110(24): E2209-18, 2013 Jun 11.
Article in English | MEDLINE | ID: mdl-23716675

ABSTRACT

Microbial capsular antigens are effective vaccines but are chemically and immunologically diverse, resulting in a major barrier to their use against multiple pathogens. A ß-(1→6)-linked poly-N-acetyl-d-glucosamine (PNAG) surface capsule is synthesized by four proteins encoded in genetic loci designated intercellular adhesion in Staphylococcus aureus or polyglucosamine in selected Gram-negative bacterial pathogens. We report that many microbial pathogens lacking an identifiable intercellular adhesion or polyglucosamine locus produce PNAG, including Gram-positive, Gram-negative, and fungal pathogens, as well as protozoa, e.g., Trichomonas vaginalis, Plasmodium berghei, and sporozoites and blood-stage forms of Plasmodium falciparum. Natural antibody to PNAG is common in humans and animals and binds primarily to the highly acetylated glycoform of PNAG but is not protective against infection due to lack of deposition of complement opsonins. Polyclonal animal antibody raised to deacetylated glycoforms of PNAG and a fully human IgG1 monoclonal antibody that both bind to native and deacetylated glycoforms of PNAG mediated complement-dependent opsonic or bactericidal killing and protected mice against local and/or systemic infections by Streptococcus pyogenes, Streptococcus pneumoniae, Listeria monocytogenes, Neisseria meningitidis serogroup B, Candida albicans, and P. berghei ANKA, and against colonic pathology in a model of infectious colitis. PNAG is also a capsular polysaccharide for Neisseria gonorrhoeae and nontypable Hemophilus influenzae, and protects cells from environmental stress. Vaccination targeting PNAG could contribute to immunity against serious and diverse prokaryotic and eukaryotic pathogens, and the conserved production of PNAG suggests that it is a critical factor in microbial biology.


Subject(s)
Acetylglucosamine/immunology , Antibodies, Bacterial/immunology , Bacterial Infections/immunology , Malaria/immunology , Mycoses/immunology , Staphylococcus aureus/immunology , Animals , Antibodies, Bacterial/pharmacology , Antibodies, Monoclonal/immunology , Antibodies, Monoclonal/pharmacology , Bacterial Capsules/immunology , Bacterial Capsules/metabolism , Bacterial Infections/microbiology , Bacterial Infections/prevention & control , Fungi/immunology , Fungi/physiology , Gram-Negative Bacteria/immunology , Gram-Negative Bacteria/physiology , Gram-Positive Bacteria/immunology , Gram-Positive Bacteria/physiology , Host-Pathogen Interactions/drug effects , Host-Pathogen Interactions/immunology , Humans , Immunoglobulin G/immunology , Immunoglobulin G/pharmacology , Malaria/parasitology , Malaria/prevention & control , Mice , Mice, Inbred C57BL , Mycoses/microbiology , Mycoses/prevention & control , Opsonin Proteins/immunology , Plasmodium berghei/immunology , Plasmodium berghei/physiology , Protein Binding/immunology , Staphylococcus aureus/metabolism , Survival Analysis , Time Factors
12.
Carbohydr Res ; 381: 161-78, 2013 Nov 15.
Article in English | MEDLINE | ID: mdl-23312144

ABSTRACT

The effect of reaction conditions, the nature of a leaving group, and a substituent at C-2 in the glycosylating monosaccharide on the stereochemical outcome of cyclization of linear tetra-ß-(1→6)-d-glucosamines and some 'mixed' tetrasaccharides comprising glucose and glucosamine residues has been examined. Toluene and nitrile solvents improved the ß-stereoselectivity of cyclization, however, the overall efficiency of the formation of cyclic products in these solvents was lower than that in dichloromethane. The use of bromide or pentenyl glycoside as leaving groups instead of the thioglycoside did not increase the ß-stereoselectivity. Replacement of the N-phthaloyl group in the glycosylating unit by N-Troc one did not affect the stereoselectivity of cyclization, while the tetrasaccharides, which contained 2-O-benzoyl glucose instead of glucosamine as the glycosyl donor moiety, were found to provide ß-linked cyclic products exclusively. Using this finding, two cyclic tetrasaccharides with alternate or adjacent arrangement of two glucose and two glucosamine units have been efficiently synthesized. These cycles were intended for the preparation of divalent glycoclusters with different ligand orientation. The difference in the stereoselectivity of cyclization of glucose and glucosamine precursors was accounted for by more effective anchimeric participation of the O-benzoyl group as compared to N-Phth and N-Troc counterparts that was confirmed by calculations of the stabilization energy and rotational barriers around C2-O/N bond in the corresponding glycosyl cations. Only the 2-O-benzoylated glycosyl cation proved to be able to form a stabilized dioxalenium intermediate, which provides stereospecific ß-glycosylation.


Subject(s)
Glucosamine/analogs & derivatives , Oligosaccharides/chemical synthesis , Carbohydrate Conformation , Contraindications , Cyclization , Glucosamine/chemical synthesis , Glucosamine/chemistry , Molecular Sequence Data , Oligosaccharides/chemistry , Quantum Theory , Stereoisomerism
13.
Carbohydr Res ; 346(15): 2499-510, 2011 Nov 08.
Article in English | MEDLINE | ID: mdl-21945383

ABSTRACT

The conformational behavior of a series of linear and cyclic oligo-(1→6)-ß-D-glucosamines and their N-acetylated derivatives, which are related to fragments of natural poly-N-acetylglucosamine, was studied by theoretical molecular modeling and experimental determination of transglycosidic vicinal coupling constants (3)J(C,H) and (3)J(H,H). Molecular dynamics simulations were performed under several types of conditions varying in the consideration of ionization of amino groups, solvent effect, and temperature. Neural network clustering and asphericity calculations were performed on the basis of molecular dynamics data. It was shown that disaccharide fragments in the studied linear oligosaccharides were not rigid, and tended to have several conformers, thus determining the overall twisted shape with helical elements. In addition, it was found that the behavior of C5-C6 bond depended significantly upon the simulation conditions. The cyclic di-, tri-, and tetrasaccharides mostly had symmetrical ring-shaped conformations. The larger cycles tended to adopt more complicated shapes, and the conformational behavior of their disaccharide fragments was close to that in the linear oligosaccharides.


Subject(s)
Acetylglucosamine/analogs & derivatives , Acetylglucosamine/chemistry , Glucosamine/analogs & derivatives , Glucosamine/chemistry , Oligosaccharides/chemistry , Carbohydrate Conformation , Carbohydrate Sequence , Magnetic Resonance Spectroscopy , Molecular Dynamics Simulation , Molecular Sequence Data
14.
Carbohydr Res ; 346(7): 905-13, 2011 May 15.
Article in English | MEDLINE | ID: mdl-21474120

ABSTRACT

A series of five 3-acetamidopropyl ß-glycosides of nona-ß-(1→6)-glucosamines containing two N-acetylglucosamine residues separated by a different number of glucosamine units with free amino groups have been synthesized using a convergent blockwise approach. Oxazoline glycosylation was used to introduce N-acetylglucosamine residues. These nonasaccharides are structurally related to the poly-N-acetylglucosamine (PNAG) extracellular polysaccharide of Staphylococcus aureus and can be used as models for biochemical and immunological studies.


Subject(s)
Acetylglucosamine/analogs & derivatives , Oligosaccharides/chemical synthesis , beta-Glucans/chemical synthesis , Acetylglucosamine/chemistry , Carbohydrate Sequence , Nuclear Magnetic Resonance, Biomolecular , Staphylococcus aureus/chemistry
15.
Infect Immun ; 78(2): 764-72, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19948836

ABSTRACT

Vaccines for pathogens usually target strain-specific surface antigens or toxins, and rarely is there broad antigenic specificity extending across multiple species. Protective antibodies for bacteria are usually specific for surface or capsular antigens. beta-(1-->6)-Poly-N-acetyl-d-glucosamine (PNAG) is a surface polysaccharide produced by many pathogens, including Staphylococcus aureus, Escherichia coli, Yersinia pestis, Bordetella pertussis, Acinetobacter baumannii, and others. Protective antibodies to PNAG are elicited when a deacetylated glycoform (deacetylated PNAG [dPNAG]; <30% acetate) is used in conjugate vaccines, whereas highly acetylated PNAG does not induce such antibodies. Chemical derivation of dPNAG from native PNAG is imprecise, so we synthesized both beta-(1-->6)-d-glucosamine (GlcNH(2)) and beta-(1-->6)-d-N-acetylglucosamine (GlcNAc) oligosaccharides with linkers on the reducing termini that could be activated to produce sulfhydryl groups for conjugation to bromoacetyl groups introduced onto carrier proteins. Synthetic 5-mer GlcNH(2) (5GlcNH(2)) or 9GlcNH(2) conjugated to tetanus toxoid (TT) elicited mouse antibodies that mediated opsonic killing of multiple S. aureus strains, while the antibodies that were produced in response to 5GlcNAc- or 9GlcNAc-TT did not mediate opsonic killing. Rabbit antibodies to 9GlcNH(2)-TT bound to PNAG and dPNAG antigens, mediated killing of S. aureus and E. coli, and protected against S. aureus skin abscesses and lethal E. coli peritonitis. Chemical synthesis of a series of oligoglucosamine ligands with defined differences in N acetylation allowed us to identify a conjugate vaccine formulation that generated protective immune responses to two of the most challenging bacterial pathogens. This vaccine could potentially be used to engender protective immunity to the broad range of pathogens that produce surface PNAG.


Subject(s)
Escherichia coli Infections/prevention & control , Peritonitis/prevention & control , Staphylococcal Skin Infections/prevention & control , Vaccines, Conjugate/immunology , beta-Glucans/immunology , Acetylation , Animals , Antibodies, Bacterial/immunology , Bacterial Capsules/immunology , Enzyme-Linked Immunosorbent Assay , Escherichia coli Infections/immunology , Humans , Mice , Peritonitis/immunology , Rabbits , Staphylococcal Skin Infections/immunology , beta-Glucans/metabolism
16.
Carbohydr Res ; 342(3-4): 567-75, 2007 Feb 26.
Article in English | MEDLINE | ID: mdl-16952342

ABSTRACT

A series of 3-beta-acetamidopropyl oligo-beta-(1-->6)-glucosamines consisting of 5, 7, 9 and 11 glucosamine residues, and a series of corresponding per-N-acetylated derivatives were synthesized using a convergent blockwise approach. These compounds represent fragments of a bacterial surface polysaccharide produced by numerous bacterial pathogens, including Staphylococcus aureus, and will be used as models for its biochemical and immunological properties.


Subject(s)
Acetylglucosamine/chemical synthesis , Glucosamine/analogs & derivatives , Glucosamine/chemical synthesis , Oligosaccharides/chemical synthesis , Acetylglucosamine/chemistry , Carbohydrate Sequence , Molecular Sequence Data
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