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Hyaluronic acid (HA) is a natural polysaccharide constructed from the alternating residues of β-D-glucuronic acid and N-acetyl-β-D-glucosamine. Being a component of glycoproteins and proteoglycans, HA performs important functions in living organisms. For example, HA plays a key role in the development of cell division and migration, vascular formation, inflammation, and oncogenesis. The review summarizes the successfully accomplished syntheses of oligosaccharides related to HA chains, an analysis of strategies for assembling the corresponding carbohydrate chains, and the evaluation of types of the used glycosyl-donors and glycosyl-acceptors, as well as strategies for choosing protective groups in the synthetic blocks. The use of enzymatic splitting of natural samples of HA and chondroitin sulfate in the work to produce appropriate low-molecular-weight oligosaccharides is also considered. Synthesized oligosaccharides and glycoconjugates based on them are valuable models for establishing a relationship between the structure and biological properties of HA and for developing approaches to the production of therapeutic drugs based on HA, including those for wound healing and treatment of inflammatory processes, as well as inhibitors of certain stages of oncogenesis. [ABSTRACT FROM AUTHOR]

The paper describes the synthesis of an aminopropyl glycoside of hexasaccharide structurally related to the branched fragment of Candida utilis glucomannan, consisting of tetra-α-(1→2)-d-mannoside, the non-reducing end of which is glycosylated with α-glucopyranose and α-mannopyranose residues attached through the (1→2) and (1→3) linkages, respectively. The target structure was assembled by block synthesis with controlled α-stereoselectivity of formation of each glycosidic bond. The resulting hexasaccharide was further converted to a biotinylated conjugate, which, together with previously synthesized similar oligosaccharides, will be used to study the antigenic properties of mannans of Candida fungi. [ABSTRACT FROM AUTHOR]

Naturally circulating antibodies could dramatically change the activity of immunogens. In some cases, cross-interference between antibodies led to the loss of their opsonizing ability. Therefore, the study of antibody repertoire in blood sera of healthy donors is helpful for the development of vaccines and diagnostic kits. Levels of antibodies to fragments of biologically significant glucosamine and galactosamine polysaccharides and their N-acetylated derivatives were first studied in blood sera of 34 healthy donors using six biotinylated carbohydrate ligands. The highest titer of antibodies was found to poly-β-(1→6)-N-acetylglucosamine (PNAG), including its fully de-N-acetylated fragment. High antibody titers to the galactosaminoglycan (GG) fragments were also detected. For both PNAG and GG, the level of antibodies to N-acetylated ligands was higher than to the ligands with free amino groups. A correlation between the antibody titers for the respective N-acetylated and N-deacetylated forms was observed, which may suggest a cross interaction. No significant amounts of the antibodies to the chitooligosaccharides were detected. The results obtained will help to rationally plan further immunological studies aimed at the development of new vaccines and diagnostic kits. [ABSTRACT FROM AUTHOR]

In the course of synthesis of oligosaccharides related to fragments of the capsular polysaccharide of Haemophilus influenzae type e, reactions of 2-O-trifluoromethanesulfonate β-D-glucopyranoside derivatives with the azide anion were studied. The reactions gave products of both nucleophilic substitution and rearrangement accompanied by 6-membered pyranose ring contraction to a 5-membered ring through (O5–C2)-cyclization. The formation of these products was interpreted for the first time using quantum mechanical calculations. [ABSTRACT FROM AUTHOR]

Glycosylation of primary (3-trifluoroacetamidopropanol) and secondary (methyl 2,3-O-isopropylidene-α-l-rhamnopyranoside) alcohols with phenyl 3,4,6-tri-O-acetyl-2-azido-2-deoxy-1-seleno-α-d-glucopyranoside in the presence of N-iodosuccinimide and trimethylsilyl triflate in diethyl ether afforded the corresponding 2-azido-2-deoxyglu-cosides in rather high yields and with good α-stereoselectivity (α:β = 3−5:1). Similar glycosylation with phenyl 3,4,6-tri-O-acetyl-2-azido-2-deoxy-1-seleno-α-d-manno-pyranoside resulted exclusively in α-linked 2-azido-2-deoxymannosides. [ABSTRACT FROM AUTHOR]

Fungal mannans are polysaccharide antigens located on the cell wall surface of various representatives of the fungal kingdom. Titers of the IgG antibodies to Candida albicans mannan are determined in the diagnosis of the candidiasis infection. Owing to high complexity and heterogeneity of the structure of natural mannans, the determination of the exact epitope structure recognized by antibodies is extremely important for the improvement of diagnostic tools based on the detection of anti-mannan antibodies. A high level of the antibodies to mannan was also found in healthy donors. However, it remains undetermined what structural epitope was recognized in this case. The levels of the IgG and IgM antibodies against individual structural fragments of mannan in the blood sera of healthy donors were determined. The anti-mannan antibody response was measured using enzyme immunoassay in a random sample of 31 blood sera of healthy donors on a panel of 11 synthetic mannooligosaccharides of various structures. A high antibody titer was found for the antigens containing the β-mannosidic bond, and the highest values were achieved in the case of two (1→2)-linked β-mannose residues. No significant level of the antibodies was revealed for antigens containing only α-mannose residues. Thus, it can be concluded that β-mannans appear to be much stronger antigens. It is assumed that the detection of antibodies to β-mannans in the sera of healthy donors can be a source of false positive results in the serological diagnosis of the Candida infection. [ABSTRACT FROM AUTHOR]

Symptoms of the new coronavirus infection that appeared in 2019 (COVID-19) range from low fever and fatigue to acute pneumonia and multiple organ failure. The clinical picture of COVID-19 is heterogeneous and involves most physiological systems; therefore, drugs with a wide spectrum of mechanism of action are required. The choice of the treatment strategy for post-COVID-19 syndrome is still a challenge to be resolved. Polysaccharides with a high fucose content derived from seaweed and marine animals can form the basis for the subsequent development of promising agents for the treatment of COVID-19 and post-COVID-19 syndrome. This class of biopolymers is characterized by a variety of biological activities, including antiviral, antithrombotic, anticoagulant, hemo-stimulating, anti-inflammatory and immune-regulatory. Low molecular weight derivatives of these polysaccharides, as well as synthetic oligosaccharides with a sufficient amount and sulfation type may be considered as the most promising compounds due to their better bioavailability, which undoubtedly increases their therapeutic potential. [ABSTRACT FROM AUTHOR]

In order to find efficient anticancer agents among natural sulfated polysaccharides and their analogs, we studied the anti-angiogenic capacity of natural fucoidans from brown algae Saccharina latissima (SL) and Chordaria flagelliformis (CF) along with chemically modified fucoidan from Punctaria plantaginea (MF) and synthetic completely sulfated fucooctasaccharide (OS) built of (1→3)-bonded residues of α-l-fucopyranose of exhibiting anti-angiogenic activity in vitro on the model of formation of capillary-like structures (precapillaries) by endothelial cells or their precursors, mesenchymal stem cells. The activity of the studied compounds was tested on cells of low-grade human breast cancer of the MDA-MB-231 line and multipotent mesenchymal stem cells (MSCs) of dogs. Fucoidan CF and its derivatives SL and MF in a concentration of 0.1 mg mL−1 reliably suppress the formation of closed circular structures by cancer cells. The formation of capillary-like structures of MSC is inhibited by fucoidan CF in concentrations of 0.1 and 0.01 mg mL−1. Modified fucoidan MF and synthetic oligosaccharide OS are somewhat less active, which can be due to their insufficiently high molecular weights and specific features of the sulfation character. The obtained data indicate that the search for anti-angiogenic agents in the series of sulfated oligosaccharides with the variation of the molecular size, structure, and sulfation pattern should be extended. [ABSTRACT FROM AUTHOR]

An extract from the knotwood of Populus tremula (quaking aspen) was studied by HPLC, NMR spectroscopy, and mass spectrometry in order to identify new sources of natural compounds as promising basis for the development of medicinal agents. The following compounds were detected and characterized in the extract: 6-O-(α-l-rhamnopyranosyl)-β-d-glucopyranosyl E-3-(4-hydroxyphenyl)acrylate, 6-O-(α-l-rhamnopyranosyl)-β-d-glucopyranosyl Z-3-(4-hydroxyphenyl)acrylate, trans-3-(4-hydroxyphenyl)acrylic acid, 7-O-(β-d-glucopyranosyl)naringenin, dihydrokaempferol, and naringenin. [ABSTRACT FROM AUTHOR]

The polysaccharide mannan is the main surface antigen of the cell wall of Candida fungi, playing an important role in the pathogenesis of diseases caused by these mycopathogens. Mannan has a complex, comb-like structure and includes a variety of structural units, with their combination varying depending on the Candida species and strain. Glucomannan, a polysaccharide from Candida utilis, contains terminal α-d-glucose residues attached to oligomannoside side chains. This paper describes the first synthesis of a pentasaccharide structurally related to C. utilis glucomannan fragment, which is an α-(1→2)-linked tetramannoside terminated at the non-reducing end by an α-d-glucopyranosyl residue. The pentasaccharide was obtained as a 3-aminopropyl glycoside, which made it possible to synthesize also its biotinylated derivative, suitable for various glycobiological studies. The most complicated step in the pentasaccharide synthesis was stereoselective 1,2-cis-glycosylation to attach the α-d-glucopyranosyl residue. This was accomplished using a glucosyl donor specially developed in our laboratory, the protecting groups of which provide the necessary α-stereoselectivity. The target biotinylated pentasaccharide thus obtained will be used in the future as a model antigen for the detection of immunodeterminant epitopes of Candida mannans. [ABSTRACT FROM AUTHOR]

This paper gives an overview of conjugate glycovaccines which contain recombinant diphtheria toxoid CRM197 as a carrier protein. A special focus is given to synthetic methods used for preparation of neoglycoconjugates of CRM197 with oligosaccharide epitopes of cell surface carbohydrates of pathogenic bacteria and fungi. Syntheses of commercial vaccines and laboratory specimen on the basis of CRM197 are outlined briefly., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Aim: Evaluation ofthe ability of capsule polysaccharides (CP) of Streptococcus pneumoniae serotype 3 and 14 and their synthetic structure analogues, conjugated with bovine serum albumin (BSA), to detect antibodies in post-vaccination sera of mice. Materials andmethods. Oligosaccharides correspond- ing to one, one and a half and two repeating links of serotype 3 and 14 S. pneumoniae CP were synthe- sized, their conjugates with BSA were produced by squarate method as well. Ligand content-per BSA molecule was controlled by MALDI-TOF spectrometry. Immune sera were obtained after 2 intraperi- toneal administrations to mice of glucoconjugates adsorbed on aluminum hydroxide or 13-valent pneumococcal conjugated vaccine. Determination of levels of post-vaccination class G antibodies and their sub-isotypes was carried out in EIA., Results: Immunization of mice with neoglucoconjugates resulted in formation of predominantly IgGl recognizing serotype 3 and 14 S. pneumoniae C. IgG1 in mice immunized with a 13-valent conjugated vaccine recognized serotype 3 S. pneumoniae CP, but detected serotype 14 S. pneumoniae CP weakly. All the conjugated synthetic oligosaccharides were characterized by a high ability to bind antibodies in blood of mice immunized with the polysaccharide conjugated vaccine. BSA-tetrasaccharide of serotype 3 S. pneumoniae and BSA-tetrasaccharide of serotype 14 S.pneumoniae were characterized by the highest ability to detect IgG1 against C., Conclusion: Synthetic oligosaccharides, conjugated with BSA protein-carrier, may be used to develop diagnostic test-systems for determination of antibodies in post-vaccination sera.

Aim: Study epitopic specificity of synthetic disaccharide, recurring link of serotype 3 S. pneumoniae, conjugated with bovine serum albumin (BSA)., Materials and Methods: Conjugate of the synthetic disaccharide with BSA was obtained by squarate method. Antigenic activity of the conjugate was studied in competitive EIA. Titers of IgG against capsule polysaccharide of serotype 3 S. pneumoniae were determined in EIA by using sera of mice immunized twice with disaccharide conjugate sorbed onto aluminum hydroxide., Results: Disaccharide conjugate used as a well-covering antigen (4 µg/well) in EIA was characterized by a high degree of specificity and interacted only with IgG against serotype 3 S. pneumoniae in antimicrobial sera of animals without reacting with antibodies (ABs) against other pneumococcus serotypes (6B, 10A, 19A, 19F, 23F). Disaccharide conjugated with BSA was determined in competitive EIA to inhibit bonding of ABs to disaccharide by 78.8%, bacterial capsule polysaccharide by 56.9%, BSA did not inhibit the sera activity. The study of sera of mice immunized by serotype 3 S. pneumoniae disaccharide conjugate in EIA, where capsule polysaccharide was used as a plate-sorbed antigen, has established the presence of IgG against capsule polysaccharide at a titer of 1:1600., Conclusion: The disaccharide that is a single recurring link of serotype 3 S. pneumoniae contains a key epitope of capsule polysaccharide. The synthetic disaccharide could be used as a component of multivalent conjugated pneumococcal vaccines and for development of diagnostic test-systems.

The blocking potency of P- and L-selectin was studied for certain small molecule mannosides and their polyacrylamide (PAA, 30 kDa) conjugates in comparison to SiaLe(x) and fucoidan. Two experimental systems were used: (1) solid phase static assay based on recombinant selectins, and (2) P-selectin dependent rat peritoneal inflammation. betaMan-SC6H4NO2- p was four times more potent P-selectin inhibitor as compared to SiaLe(x). Docking of this molecule onto the P-selectin carbohydrate-binding site demonstrated that a nitro group enabled an electrostatic interaction with residue Lys 84, while the phenyl ring and the CH2 at C-6 contacted the CH2 groups of the same Lys residue. In vivo, betaMan-SC6H4NO2- p blocked experimental inflammation better than SiaLe(x), but significantly lower than fucoidan. In vitro Man-polyacrylic acid conjugates appeared to be very potent inhibitors comparable to fucoidan, uncharged Man-PAA proved rather active, comparable to SiaLe(x)-PAA both in vitro, and in vivo, whereas mannan did not display any P-selectin blocking effect.