Synthesis of a Pentasaccharide and Neoglycoconjugates Related to Fungal α‐(1→3)‐Glucan and Their Use in the Generation of Antibodies to Trace <i>Aspergillus fumigatus</i> Cell Wall

Komarova, Bozhena S.; Orekhova, Maria V.; Tsvetkov, Yury E.; Beau, Rémi; Aimanianda, Vishukumar; Latgé, Jean‐Paul; Nifantiev, Nikolay E.

doi:10.1002/chem.201404770

Cited by 61 publications

(42 citation statements)

References 37 publications

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“…Disaccharide glucosyl donor 162 , bearing a remote stereodirecting benzoyl group at O‐6 of reducing glucose, was also used in the synthesis of a pentasaccharide related to the fragment of the α‐(1→3)‐glucan from Aspergillus fumigatus (Scheme ) …”

Section: Design Of α‐Selective Glycopyranosyl Donors Relying On Remotmentioning

confidence: 99%

Design of α-Selective Glycopyranosyl Donors Relying on Remote Anchimeric Assistance

Komarova

Tsvetkov

Nifantiev

2016

The Chemical Record

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102

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Oligosaccharides have a variety of versatile biological effects, but unlike peptides and oligonucleotides, investigation of the roles of oligosaccharides is not easy. Since biosynthesis of oligosaccharides does not comply with direct genetic control, their isolation from natural sources and biotechnological preparation are complicated, due to the heterogeneous composition of raw carbohydrates. Oligosaccharide synthesis is needed for the establishment or confirmation of the structure of natural glycocompounds. Also, synthetically prepared, defined oligosaccharides and their derivatives are becoming increasingly important tools for many biological and immunological research projects. The key step of oligosaccharide synthesis involves glycosylation, a reaction that builds glycosidic bonds. Usually, construction of 1,2-trans-bonds is easy, and therefore, this reaction can even be included into automated syntheses. At this time, installation of the 1,2-cis-bond remains simultaneously frustrating and compelling. In our and other laboratories, a strategy of α-selective (1,2-cis) glycosylation, relying on remote anchimeric assistance with acyl groups, is studied. The state of the art in this work is summarized in this review.

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Section: Design Of α‐Selective Glycopyranosyl Donors Relying On Remotmentioning

confidence: 99%

Design of α-Selective Glycopyranosyl Donors Relying on Remote Anchimeric Assistance

Komarova

Tsvetkov

Nifantiev

2016

The Chemical Record

Self Cite

102

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“…First, the glycans carrying an amino terminated linker at their reducing end were synthesized by multi-step chemo-enzymatic synthesis as previously reported [ 65 , 67 ]. Chemical conjugation to lysine residues of BSA was accomplished by homobifunctional amino-reactive linker squaric acid diethyl ester enabling crosslinking via primary amino groups [ 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 ]. Variation of the molar ratios of glycan with respect to lysine residues resulted in the synthesis of 11 neo-glycoproteins of both types with different degrees of glycan modification.…”

Section: Introductionmentioning

confidence: 99%

Galectin Binding to Neo-Glycoproteins: LacDiNAc Conjugated BSA as Ligand for Human Galectin-3

2015

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Carbohydrate-lectin interactions are relatively weak. As they play an important role in biological recognition processes, multivalent glycan ligands are designed to enhance binding affinity and inhibitory potency. We here report on novel neo-glycoproteins based on bovine serum albumin as scaffold for multivalent presentation of ligands for galectins. We prepared two kinds of tetrasaccharides (N-acetyllactosamine and N,N-diacetyllactosamine terminated) by multi-step chemo-enzymatic synthesis utilizing recombinant glycosyltransferases. Subsequent conjugation of these glycans to lysine groups of bovine serum albumin via squaric acid diethyl ester yielded a set of 22 different neo-glycoproteins with tuned ligand density. The neo-glycoproteins were analyzed by biochemical and chromatographic methods proving various modification degrees. The neo-glycoproteins were used for binding and inhibition studies with human galectin-3 showing high affinity. Binding strength and inhibition potency are closely related to modification density and show binding enhancement by multivalent ligand presentation. At galectin-3 concentrations comparable to serum levels of cancer patients, we detect the highest avidities. Selectivity of N,N-diacetyllactosamine terminated structures towards galectin-3 in comparison to galectin-1 is demonstrated. Moreover, we also see strong inhibitory potency of our scaffolds towards galectin-3 binding. These novel neo-glycoproteins may therefore serve as selective and strong galectin-3 ligands in cancer related biomedical research.

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“…Ранее было установлено, что иммунизация лабораторных мышей конъюгатом (1→3)-глюкозидного лиганда с бычьим сывороточным альбумином вызывает выработку специфических антител, которые распознают поверхностные олигосахариды Aspergillus fumigatus [7]. Результаты, полученные в нашей работе, согласуются с указанными данными.…”

Section: Discussionunclassified

Antigenic Activity Assays of Experimental Conjugate Vaccines Based on Synthetic Oligosaccharide Ligands and Crm197 Carrier Protein

et al. 2017

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So far, there is no effective treatment for a number of socially significant bacterial and fungal diseases. β-(1→3) glucans are polysaccharides consisting of glucose units linked together with β-(1→3)glycoside bonds. They are principal components of the fungal cell wall including such dangerous nosocomial pathogens as Candida albicans, Aspergillus fumigatus and others. At the same time, β-(1→3) glucans are absent in humans and other mammals, thus making them to be promising components of carbohydrate-protein conjugate vaccines for prevention and treatment of fungal infections. The CRM197 protein is a non-toxic derivative of diphtheria toxin, which is widely used as a safe carrier for conjugate vaccines. The CRM197 extraction from lysogenic C. diphtheriae cultures is a classic way of its production. An alternative to the classic method is a transgene-driven CRM197 protein expression in E. coli, B. subtilis and Pseudomonas fluorescens. The advantage for using Escherichia coli in this case is that this method is more simple and inexpensive, and allows of producing recombinant CRM197 within short terms employing a non-pathogenic microorganism. The purpose of this study was to investigate antigenic activity in the samples of experimental conjugate vaccines based on synthetic oligosaccharide ligands and CRM197 carrier protein, by means of a competitive ELISA. A double immunization of laboratory Balb/c mice with experimental samples of conjugate vaccines based on oligosaccharide ligands and CRM197 protein caused induction of specific antibodies at high titers. All the samples of oligoglucoside-based conjugate vaccines with different contents of monomeric units (pentasaccharides, heptasaccharides, nanosaccharides, and undecasaccharides) caused the formation high antibody titer at the level 1: 51,200,following tandem injections. High avidity of antibodies to their oligosaccharide ligands was shown by competitive ELISA reaction. These data suggest a relevance of further pre-clinical trials of conjugate vaccines against Candida and Aspergillus, as well as selection of the most immunogenic and effective version of the conjugate vaccine.

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Synthesis of a Pentasaccharide and Neoglycoconjugates Related to Fungal α‐(1→3)‐Glucan and Their Use in the Generation of Antibodies to Trace Aspergillus fumigatus Cell Wall

Cited by 61 publications

References 37 publications

Design of α-Selective Glycopyranosyl Donors Relying on Remote Anchimeric Assistance

Design of α-Selective Glycopyranosyl Donors Relying on Remote Anchimeric Assistance

Galectin Binding to Neo-Glycoproteins: LacDiNAc Conjugated BSA as Ligand for Human Galectin-3

Antigenic Activity Assays of Experimental Conjugate Vaccines Based on Synthetic Oligosaccharide Ligands and Crm197 Carrier Protein

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