RESUMO
As part of a continuing study aimed to achieve improved monoclonal antibodies against carcinoembryonic antigen (CEA) carbohydrate fragments, the synthesis of a sialyl-(2-->6)-lactosamine trisaccharide with a 5-amino-3-oxapentyl spacer group at C-1I has been developed. Two different routes to access this target are described. For this purpose 5-azido-3-oxapentyl 6-O-benzyl-2-deoxy-2-phthalimido-beta-D-glucopyranoside (4) was selectively beta-galactosylated in 81% yield using the crystalline 2,3-di-O-acetyl-4,6-O-benzylidene-alpha-D-galactopyranosyl trichloroacetimidate as the donor, taking advantage of the bulky phthalimido group at C-2 of 4. On the other hand, galactosylation of the suitable protected acceptor 5-azido-3-oxapentyl 2-acetamido-3,6-di-O-benzyl-2-deoxy-beta-D-glucopyranoside with the crystalline 2,3-di-O-acetyl-4,6-O-benzylidene-alpha-D-galactosyl bromide renders the corresponding disaccharide in a moderate 58% yield. Despite the fact that the first strategy, unlike the second one, requires a hydrazinolysis-acetylation reaction at the disaccharide stage, it was found to be more convenient to access the disaccharide acceptor. Sialylation was performed using a thiophenyl donor under an NIS-TfOH activation procedure in acetonitrile to give a mixture of alpha and beta trisaccharides in 49 and 16% yields, respectively.
Assuntos
Trissacarídeos/síntese química , Anticorpos Monoclonais , Configuração de Carboidratos , Sequência de Carboidratos , Antígeno Carcinoembrionário/química , Antígeno Carcinoembrionário/imunologia , Indicadores e Reagentes , Modelos Moleculares , Dados de Sequência Molecular , Trissacarídeos/químicaRESUMO
Vibrio cholerae O1 LPS terminal mono- and disaccharide elements were synthesized by reduction of the azido group in several 4-amino-4,6-dideoxy-D-mannose mono- and disaccharide derivatives, followed by coupling with 2, 4-di-O-acetyl-3-deoxy-L-glycero-tetronic acid in the presence of 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline. This compound represents a useful model in order to elucidate the size of the epitopes which define Ogawa and Inaba serotypes from Vibrio cholerae O1.
Assuntos
Antígenos de Bactérias/química , Dissacarídeos/síntese química , Epitopos/química , Hidroxibutiratos/síntese química , Lipopolissacarídeos/química , Vibrio cholerae/imunologia , Animais , Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/imunologia , Configuração de Carboidratos , Dissacarídeos/química , Dissacarídeos/imunologia , Ensaio de Imunoadsorção Enzimática , Hidroxibutiratos/química , Camundongos , Monossacarídeos/síntese química , Monossacarídeos/química , Monossacarídeos/imunologia , Rotação Ocular , Sorotipagem , Vibrio cholerae/classificaçãoRESUMO
5-Azido-3-oxa-pentyl beta-D-galactopyranoside was prepared from diethylene glycol monochlorohydrin and used as a model of oligosaccharide hapten. After deprotection, a series of amides bearing thiophilic groups had been obtained through the terminal amino function and essayed in coupling reactions with thiolated BSA. Also several Lewis human blood group oligosaccharides had been conjugated with thiolated BSA demonstrating the usefulness of the methodology.
Assuntos
Glicosídeos/química , Proteínas/química , Compostos de Sulfidrila/química , Configuração de Carboidratos , Sequência de Carboidratos , Humanos , Espectroscopia de Ressonância Magnética , Dados de Sequência MolecularRESUMO
Following the chemical isolation and characterization of the glycolipid phenolic I by Hunter and Brennan in 1981, derived from infected armadillo liver, studies were continued to achieve the chemical synthesis of this trisaccharide, which is part of the glycolipid and, as it has been demonstrated, was the major antigenic determinant of this substance. The synthetic antigen obtained by Fujiwara in 1984 and Gigg in 1985, was conjugated with bovine albumin. Immunodominance of the terminal residue 3,6-Di-O-methyl-glucose was confirmed by the use of ELISA, monoclonal and polyclonal antibodies. In Cuba, Mariño and Verez, based on this knowledge obtained the antigen by another way of synthesis conjugated with acrylamide against positive and negative (71%) control sera, as well as its specificity in the reaction with sera from tuberculous patients and children vaccinated with BCG (89%).
Assuntos
Antígenos de Bactérias/imunologia , Glicolipídeos/imunologia , Mycobacterium leprae/imunologia , Vacinas Sintéticas/imunologia , Vacinas/imunologia , Epitopos/imunologia , HumanosRESUMO
The trisaccharide allyl O-(3,4-di-O-methyl-beta-D-glucopyranosyl)-(1----4)-O-(2,3-di-O-methyl-al pha-L- rhamnopyranosyl)-(1----2)-3-O-methyl-alpha-L-rhamnopyranoside was synthesized from partially methylated monosaccharide derivatives. Condensation of 1,4-di-O-acetyl-2,3-di-O-methyl-alpha-L-rhamnopyranose promoted by boron trifluoride etherate with the appropriate alcohol proceeded stereoselectively and with very high yields. Selective deacetylation and glycosylation with 2,4-di-O-acetyl-3,6-di-O-methyl-alpha-D-glucopyranosyl bromide led to a trisaccharide. The acrylamide copolymers of mono-, di-, and tri-saccharide were compared in their ability to specifically bind antibodies from leprosy patients.