[Affect of deoxynojirimycin derivatives on hepatitis C virus morphogenesis].

Viral hepatitis C is one of the wide-spread and dangerous human diseases. The choice of drugs for treatment of chronic hepatitis C virus (HCV) infection is limited and prophylactic vaccines do not exist. Thus, the development of new antiviral strategies and substances are of great importance. The targeting of viral morphogenesis might be used as an alternative approach to existing strategies of HCV blocking. The glycosylation of viral envelope proteins is an important step of viral particle morphogenesis that determines the correct assembly of HCV virions. The derivatives of glucose analog deoxynojirimycin (DNJ)--inhibitors of alpha-glucosidase can impair the assembly of structural proteins and HCV particle formation. In the present work the affect of alkylated derivatives of DNJ N-pentyl-DNJ and N-benzyl-DNJ to HCVmorphogenesis in a model system insect cells producing three viral structural proteins with formation of virus-like particles was studied. Intracellular N-glycosylation of HCV envelope glycoproteins was shown to be impaired by DNJ derivatives. At 1 mM concentrations of these substances the level of gpE1 and gpE2 glycoproteins increase and their electrophoretic mobility decrease which seems to be due to inhibition of a-glucosidase in endoplasmic reticulum and accumulation of hyperglycosylated N-glycans in HCV glycoproteins. The interaction of the latters with calnexin leads to formation of unproductive dimers and bloks productive assembly of virus-like particles.

[Trityl-cyanoethylidene condensation of azidosaccharide derivatives as a route to hexosaminoglycans. Synthesis of the O-antigenic polysaccharide of Pseudomonas aeruginosa X (Meitert)]. / Tritil-tsianoétilidenovaia kondensatsiia proizvodnykh azidosakharov kak put' k geksozaminoglikanam. Sintez O-antigennogo polisakharida Pseudomonas aeruginosa X (Meitert).

Derivatives of azidosugars were shown to be stable under conditions of trityl-cyanoethylidene condensation. Tritylated 1,2-O-(1-cyano)ethylidene derivative of 2-azido-2-deoxy-beta-D-mannopyranosyl-(1----4)-L-rhamnopyranose was used as a starting material for the synthesis of [----3)-beta-D-ManNAc-(1----4)-alpha-L-Rha-(1----]n, the O-specific polysaccharide of Pseudomonas aeruginosa X (Meitert).

[Antibodies to the rhamnose determinants of the polysaccharide of streptococci group A in the sera of rheumatism patients and donors]. / Antitela k ramnoznym determinantam polisakharida streptokokkov gruppy A v syvorotkakh bol'nykh revmatizmom i donorov.

In the sera of patients with recurrent rheumocarditis, and especially in cases of primary rheumatism, the level of antibodies to group A streptococcal polysaccharide (A-PS) has been found, according to the results of the enzyme immunoassay, to be considerably higher than in the sera of healthy donors. The level of antibodies to rhamnose determinants (RD) of A-PS has been determined by the inhibition of the immunoenzyme reaction with A-PS under the influence of a variant of group A streptococcus and rhamnose disaccharides with the bonds alpha 1-2 and alpha 1-3. In patients with recurrent rheumocarditis the level of antibodies to A-PS has been shown to be considerably higher than in healthy donors having these antibodies. In acute primary rheumatism a high level of antibodies to A-PS has been detected only in a few cases, and at the same time the prevalence of antibodies to the specific RD of A-PS, bound with beta-N-acetylglucosamine, is observed. In the sera of patients with recurrent rheumocarditis and donors having a high content of antibodies to the rhamnose site of A-PS antibodies, seemingly active against at least two RD, have been detected. In acute primary rheumatism an insignificant amount of antibodies to the rhamnose site of A-PS may probably cause the autoimmune process accompanying rheumatism. This suggestion is substantiated by the previously established capacity of these antibodies for inducing the suppression of cytotoxic cell reactions to microbial antigens.

[Synthesis of the polysaccharide common antigen of Pseudomonas aeruginosa and its L-analog in the form of 6-aminohexyl glycosides]. / Sintez polisakharidnogo obshchego antigena Pseudomonas aeruginosa i ego L-analoga v forme (6-aminogeksil)glikozidov.

A synthesis of trisaccharide monomers built of D- or L-rhamnose residues is described. Their polycondensation in the presence of a 6-aminohexyl rhamnoside derivative afforded 6-aminohexyl glycosides of the natural common polysaccharide antigen of Pseudomonas aeruginosa and its L-analogue, respectively.

[Synthesis of 6-aminohexylglycosides of a polysaccharide from Streptococcus group A and its fragments]. / Sintez 6-aminogeksilglikozidov polisakharida streptokokkov gruppy A-variant i ego fragmentov.

Polycondensation of 4-O-benzoyl-1,2-O-(1-cyanoethylidene)-3-O-(3,4-di-O-benzoyl-2-O-tr ityl-alpha-L- rhamnopyranosyl)-beta-L-rhamnopyranose in the presence of 6-phthalimidohexyl-3,4-di-O-benzoyl-2-O-trityl-alpha-L- rhamnopyranoside affords, after deprotection, the polysaccharide built up of the repeating dissaccharide units----2) Rha (alpha 1----3) Rha (alpha 1----and containing 6-aminohexyl residue at the reducing end. This polysaccharide possesses the structure of the group A-variant streptococcal polysaccharide. Synthesis of 6-aminohexyl glycosides of 2- and 3-O-alpha-L-rhamnopyranosyl-alpha-L-rhamnopyranoses, which corresponds to the repeating units of the above polysaccharide, is described.

[Synthesis of capsular polysaccharide of Streptococcus pneumoniae type 14. 3. Synthesis of a monomer for polycondensation]. / Sintez kapsuliarnogo polisakharida Streptococcus pneumoniae, tip 14. 3. Sintez monomera dlia polikondensatsii.

Synthesis of a tritylated tetrasaccharide 1,2-O-(1-cyano) ethylidene derivative is described by glycosylation of 3,6-di-O-benzoyl-4-O-(2,4,6-tri-O-benzoyl-beta- D-galactopyranosyl)-1,2-O-[1-(exo-cyano)ethylidene]-alpha-D- glucopyranose with 6-O-acetyl-3-O-benzoyl-4-O-(2,3,4,6-tetra-O-benzoyl-beta- D-galactopyranosyl)-2-deozy-2-phthalimido-D-glucopyranosyl. bromide followed by selective deacetylation and tritylation.

[Synthesis of capsular polysaccharide of Streptococcus pneumoniae type 14. 4. Polycondensation of the monomer and characteristics of the polysaccharide]. / Sintez kapsuliarnogo polisakharida Streptococcus pneumoniae, tip 14. 4. Polikondensatsiia monomera i kharakteristika polisakharida.

Synthesis of a regular branched polysaccharide [6(Gal beta 1-4)GlcNAc beta 1-3Gal beta 1-4Glc beta 1]n whose structure corresponds to that of the capsular polysaccharide of Streptococcus pneumoniae type 14, is described, involving a stereospecific polycondensation of the tetrasaccharide monomer, deacylation, and N-acetylation.

[Synthesis of the capsular polysaccharide of Streptococcus pneumoniae type 14. 1. Synthesis of a derivative of the tetrasaccharide repetitive link]. / Sintez kapsuliarnogo polisakharida Streptococcus pneumoniae, tip 14. 1. Sintez proizvodnogo tetrasakharidnogo povtoriaiushchegosia zvena.

A branched tetrasaccharide derivative of the repeating unit of the capsular polysaccharide of Streptococcus pneumoniae type 14 has been synthesised by condensation of per-O-benzoylated 1,2-O-(1-cyano)ethylidene derivative of lactose with 6-O-tritylated methyl lactosaminide.

[Synthesis of the capsular polysaccharide of Streptococcus pneumoniae type 14. 2. Synthesis of methyl-6-O-acetyl-4-O-(2,3,46-tetra-O-benzoyl -beta-D-galactosylpyranosyl)-2-deoxy-2-phthalimido-beta-D-gluco- pyranoside--a lactosamine precursor in the monomer synthesis for polycondensation]. / Sintez kapsuliarnogo polisakharida Streptococcus pneumoniae, tip 14. 2. Poluchenie metil-6-O-atsetil-3-O-benzoil-4-O-(2,3,4,6-tetra-O- benzoil-beta-D-galaktopiranozil)-2-dezoksi-2-ftalimido-beta-D- gliukopiranozila--laktozaminnogo predshestvennika v sinteze monomera dlia polikondensatsii.

Glycosylation of methyl 6-O-acetyl-3-O-benzoyl-2-deoxy-phthalimido-beta-D-glucopyranoside and its 4-trityl ether by benzobromogalactose, 1-O-acetyl-2,3,4,6-tetra-O-benzoyl-beta-D-galactopyranose, 1,2-[(alpha-p-tolylthio)benzylidene]- and 1,2-O-[(alpha-cyano)benzylidene]-3,4,6-tri-O-benzoyl-alpha-D- galactopyranoses proceeds non-stereospecifically. The best yield of beta-linked disaccharide was obtained upon glycosylation by benzobromogalactose in the presence of silver triflate and tetramethylurea in nitromethane.

[Synthesis of the capsular polysaccharide of Streptococcus pneumoniae type 14]. / Sintez kapsuliarnogo polisakharida Streptococcus pneumoniae, tip 14.

Synthesis of the regular branched polysaccharide [-6(Gal beta 1-4)GlcNAc beta 1-3Gal beta 1-4Glc beta 1-]n structurally corresponding to capsular polysaccharide of Streptococcus pneumoniae type 14 involves blockwise synthesis of a tritylated 1,2-O-(1-cyano)ethylidene tetrasaccharide derivative from lactosamine and lactose precursors followed by stereospecific polycondensation of the tetrasaccharide monomer.

[Synthesis of a repeating unit and the dimer of the repeating unit of the major chain of Shigella flexneri O-antigen polysaccharide]. / Sintez povtoriaiushchegosia zvena i dimera povtoriaiushchegosia zvena osnovnoi tsepi O-antigennykh polisakharidov Shigella flexneri.

Methyl glycoside of the tetrasaccharide GlcNAc(beta 1-2)Rha(alpha 1-2)Rha(alpha 1-3)Rha, which represents a repeating unit of the basic chain of Shigella flexneri O-antigenic polysaccharides, was synthesized using acylated monosaccharide synthons. A dimer of the repeating unit, octasaccharide [GlcNAc(beta 1-2)Rha(alpha 1-2) Rha(alpha 1-3)Rha(alpha 1-3)]2-OMe was obtained by TrClO4-catalyzed condensation of two tetrasaccharide blocks.

[Synthesis of oligosaccharide fragments of O-specific polysaccharides of Shigella flexneri. III. Synthesis of the tetrasaccharide Glc alpha 1-3Rha alpha 1-2(Glc alpha 1-3)Rha alpha 1-OMe and the pentasaccharide GlcNAc beta 1-2(Glc alpha 1-3)Rha alpha 1-2(Glc alpha 1-3)Rha alpha 1-OMe]. / Sintez oligosakharidnykh fragmentov O-spetsificheskikh polisakharidov shigella flexneri. III. Sintez tetrasakharida Glc alpha 1-3Rha alpha 1-2(Glc alpha 1-3)Rha alpha 1-OMe i pentasakharida GlcNAc beta 1-2 (Glc alpha 1-3)Rha alpha 1-2(Glc alpha 1-3)Rha alphal-OMe.

Two synthetic schemes to prepare the title branched tetrasaccharide and pentasaccharide are described. These oligosaccharides represent fragments of the O-antigenic polysaccharides of Shigella flexneri serotype 5b.

[Synthesis of oligosaccharide fragments of O-specific Shigella flexneri polysaccharides. II. Synthesis of trisaccharide Glc alpha1----3RHa alpha1----2Rha alpha1----OMe and tetrasaccharide GlcNAc beta1----2(Llc alpha1----3)Rha alpha1----2Rh alpha1----OMe]. / Sintez oligosakharidnykg fragmentov O-spetsificheskikh polisakharidov Shigella flexneri. II. Sintez trisakharida Glc alpha1----3Rha alpha1----OMe i tetrasakharida GlcNAc beta1----2(Glc alpha----3)Rha alpha1----OMe.

Methyl glycosides of the title linear trisaccharide and branched tetrasaccharide were synthesized by stepwise glycosylation. These oligosaccharides represent the fragments of O-antigenic polysaccharides of Shigella flexneri serotypes 2b, 3a, 5b, and X.

[Immunochemical analysis of oligosaccharide fragments of O-specific Shigella flexneri polysaccharides]. / Immunokhimicheskii analiz oligosakharidnykh fragmentov O-spetsificheskikh polisakharidov Shigella flexneri.

Comparison of inhibitory properties of several synthetic oligosaccharides related to Sh. flexneri O-specific polysaccharides, namely Glc alpha 1-3Rha alpha 1-OMe, Glc alpha 1-3Rha alpha 1-2Rha alpha 1-OMe, Rha alpha 1-2(Glc alpha 1-3)Rha alpha 1-OMe, GlcNAc beta 1-2(Glc alpha 1-3)Rha alpha 1-OMe, and GlcNAc beta 1-2(Glc alpha 1-3) Rha alpha 1-2Rha alpha 1-OMe, using passive haemagglutination reaction demonstrated the tetrasaccharide to possess the highest activity in V; 7,8-anti-7,8 immune system. Among the oligosaccharides under study, only Rha alpha 1-2(Glc alpha 1-3)Rha alpha 1-OMe exhibited moderate anti-V activity.