Synthesis and Immunological Screening of β‐Linked Mono‐ and Divalent Mannosides

Mukherjee, Chinmoy; Ranta, Kaarina; Savolainen, J.; Leino, Reko

doi:10.1002/ejoc.201200041

Cited by 11 publications

(14 citation statements)

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“…The hydroxylated analogues of these compounds ( 21 – 23 , 27 – 29 , 33 – 35 , 39 – 41 , and 45 – 47 ) were then obtained by sodium methoxide‐mediated mild saponification (Scheme ). We had previously synthesized compounds 21 – 23 and some of their corresponding divalent analogues (non‐scaffold‐based) by a different synthetic route 31. The prepared mono‐ and divalent mannosides were then further biologically evaluated in a competitive inhibition enzyme‐linked immunosorbent assay (ELISA), with some compounds showing moderate inhibition capacity of specific human IgG binding to low‐molecular‐weight Candida albicans mannan.…”

Section: Resultsmentioning

confidence: 99%

Chemistry and Biology of Oligovalent β‐(1→2)‐Linked Oligomannosides: New Insights into Carbohydrate‐Based Adjuvants in Immunotherapy

Mukherjee¹,

Mäkinen²,

Savolainen³

et al. 2013

Chemistry A European J

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A series of oligovalent carbohydrate assemblies (ranging from mono- to pentavalent), derived from three structurally different β-linked or β-(1→2)-linked mannosides, has been chemically synthesized, and the respective compounds have been biologically evaluated in order to investigate their immunostimulatory properties. The Crich methodology for β-mannosylation was successfully utilized to introduce the β-linkages, and a click chemistry protocol was utilized to generate the oligovalent derivatives. A convenient protecting group strategy involving the simultaneous use of both p-methoxybenzyl and benzylidene groups was employed, which allowed a simple and cost-effective global deprotection step. The immunomodulatory properties of the synthesized multivalent mannosides were evaluated by assessing cytokine production in human white blood cell cultures. The Th2-type cytokines interleukin-4 and interleukin-5 (IL-4 and IL-5), the Th1 cytokine interferon-γ (IFN-γ), the Treg cytokine IL-10, and the pro-inflammatory cytokine tumor necrosis factor (TNF) were included in the screening. A single trivalent acetylated mannobiose derivative was identified as a potent inducer of Treg and Th1 immune response, resulting in strong IL-10 and moderate IFN-γ productions dose-dependently, while inducing no Th2 cytokine response. The immunomodulatory properties of this trivalent mannoside were further studied in vitro in allergen (Bet v)-stimulated human peripheral blood mononuclear cell cultures of birch pollen allergic subjects. Stimulation with birch pollen induced strong IL-4 and IL-5 responses, which could be suppressed by the trivalent acetylated mannobiose derivative. The IL-10 response was also suppressed, whereas the production of IFN-γ was strongly enhanced. The results suggest that the identified lead compound has suppressive effects on the Th2-type allergic inflammatory response and shows potential as a possible lead adjuvant for the specific immunotherapy of allergies.

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Section: Resultsmentioning

confidence: 99%

Chemistry and Biology of Oligovalent β‐(1→2)‐Linked Oligomannosides: New Insights into Carbohydrate‐Based Adjuvants in Immunotherapy

Mukherjee¹,

Mäkinen²,

Savolainen³

et al. 2013

Chemistry A European J

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“…[36,37] Althoughi nt he present case the possible influence of the triazole moiety on the biological activity of the glycoclusters 1-3 cannotb er uled out completely,i tm ust be emphasized that out of av ery large number of oligovalent b-(1!2) mannosides screened during our previous investigations, [17][18][19] of which several othersa lso contained triazole units, the only compound showingp romising in vitro activity was compound 1 and now www.chemmedchem.org here its analogues 2 and 3.C ommon features shared by these three active compounds are:1 )fully acetylatedt rivalent b-(1! This makes them accessible for biological targets,a nd it is known that triazoles can take part in biological events.…”

Section: Compoundmentioning

confidence: 92%

Acetylated Trivalent Mannobioses: Chemical Modification, Structural Elucidation, and Biological Evaluation

et al. 2016

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People suffering from allergies can be treated with repeated injections of increasing amounts of a specific allergen. This type of specific immunotherapy is currently the only way to treat the underlying pathological immune response associated with an allergy. The approach can afford long-lasting protection, but the process takes 3-5 years, can produce allergic reactions, and in severe cases treatment is often aborted due to anaphylaxis. However, treatment can be optimized with the use of specific adjuvants that modify the immune response, its duration, and that increase the production of the correct type of antibodies. In the pursuit of such adjuvants, two new trivalent acetylated β-(1→2)-linked mannobioses based on a previously discovered lead molecule were prepared. The new molecules, along with the previously developed lead, were investigated by rigorous NMR and molecular modeling experiments in order to elucidate their behavior and preferred conformations in solution. Furthermore, the molecules were subjected to a biological investigation in which their immunostimulatory properties were evaluated by assessing their effect on the production of TH 2-type cytokine interleukin-4 (IL-4) and Treg pro-inflammatory cytokine tumor necrosis factor (TNF). Treatment of peripheral mononuclear blood cell cultures from patients suffering from birch allergy with birch allergen Bet v induced a strong IL-4 response, whereas the same treatment together with the trivalent acetylated mannobioses caused significant suppression of the induced IL-4.

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“…The disaccharide intermediates were synthesized from the suitably protected monosaccharide derivatives 2 [13], 3 [14], 4 [15] and 5 [16], which were prepared from the commercially available reducing sugars, by applying a series of functional group protection–deprotection methodologies (Fig. 2).…”

Section: Resultsmentioning

confidence: 99%

“…2). The synthetic strategy has a number of notable features, which include (a) stereoselective [2 + 2] block glycosylation; (b) application of general glycosylation reactions by using thioglycosides as glycosyl donors and a combination of N -iodosuccinimide (NIS) and perchloric acid supported over silica (HClO 4 –SiO 2 ) [17–18] as glycosyl activator; (c) exploitation of the armed–disarmed glycosylation concept for the orthogonal activation of thioglycoside during the synthesis of disaccharide derivative 9 [19]; (d) use of aminoethyl linker as the anomeric protecting group; (e) removal of benzyl groups using a combination of triethylsilane and Pd(OH) 2 –C [20]; and (f) preparation of β-D-mannosidic moiety from the β-D-glucoside [13]. …”

Section: Resultsmentioning

confidence: 99%

“…Benzylation of 2-azidoethyl 3- O -benzyl-4,6- O -benzylidene-β-D-mannopyranoside ( 2 ) [13] (prepared from D-glucose in nine steps) by using benzyl bromide and sodium hydroxide [21] followed by reductive ring opening of the 4,6- O -benzylidene acetal with triethylsilane and iodine [22] furnished compound 6 in 82% yield. Stereoselective glycosylation of compound 6 with thioglycoside derivative 3 in the presence of a combination of N -iodosuccinimide (NIS) and HClO 4 –SiO 2 [17] gave disaccharide derivative 7 in a 77% yield.…”

Section: Resultsmentioning

confidence: 99%

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Convergent synthesis of the tetrasaccharide repeating unit of the cell wall lipopolysaccharide of Escherichia coli O40

Misra

2012

Beilstein J. Org. Chem.

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SummaryA tetrasaccharide repeating unit corresponding to the cell-wall lipopolysaccharide of E. coli O40 was synthesized by using a convergent block glycosylation strategy. A disaccharide donor was coupled to a disaccharide acceptor by a stereoselective glycosylation. A 2-aminoethyl linker was chosen as the anomeric protecting group at the reducing end of the tetrasaccharide. All glycosylation steps are significantly high yielding and stereoselective.

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Synthesis and Immunological Screening of β‐Linked Mono‐ and Divalent Mannosides

Cited by 11 publications

References 65 publications

Chemistry and Biology of Oligovalent β‐(1→2)‐Linked Oligomannosides: New Insights into Carbohydrate‐Based Adjuvants in Immunotherapy

Chemistry and Biology of Oligovalent β‐(1→2)‐Linked Oligomannosides: New Insights into Carbohydrate‐Based Adjuvants in Immunotherapy

Acetylated Trivalent Mannobioses: Chemical Modification, Structural Elucidation, and Biological Evaluation

Convergent synthesis of the tetrasaccharide repeating unit of the cell wall lipopolysaccharide of Escherichia coli O40

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