Synthesis of monodeoxy and mono-O-methyl congeners of methyl β-d-mannopyranosyl-(1→2)-β-d-mannopyranoside for epitope mapping of anti-Candida albicans antibodies

Nycholat, Corwin M.; Bundle, David R.

doi:10.1016/j.carres.2008.12.011

Cited by 14 publications

(8 citation statements)

References 23 publications

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“…In contrast, functionalization of the C3 position has been observed for the substrate-controlled reactions of the b-d-glucose-derived 2,3-diols. [12] Because of the low solubility of the precursor to 4 b, its reaction with dihydropyran was significantly slower than those leading to 3 a and 4 a, even at 0 8C. While the reaction catalyzed by (R)-2 d provided 4 b (entry 3, C2/C3 = 6:1), the reaction catalyzed by (S)-2 d was sluggish and favored formation of the C3protected isomer (C2/C3 = 1:2.6).…”

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confidence: 99%

Chiral Phosphoric Acid Directed Regioselective Acetalization of Carbohydrate‐Derived 1,2‐Diols

et al. 2013

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Chiral Phosphoric Acid Directed Regioselective Acetalization of Carbohydrate‐Derived 1,2‐Diols

et al. 2013

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“…The syntheses of disaccharides modified at the reducing monosaccharide (internal) residue, compounds 2−7, have been described. 25 Syntheses of disaccharide 1 and disaccharides modified at the nonreducing (terminal) mannose 8−15, as well as trisaccharides 16−18, are given in brief outline with full details in the Supporting Information. The synthesis of three trisaccharide congeners 19−21 is reported separately.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Design of a Candida albicans Disaccharide Conjugate Vaccine by Reverse Engineering a Protective Monoclonal Antibody

et al. 2012

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A disaccharide-chicken serum albumin conjugate vaccine against Candida albicans infections has been developed by reverse engineering a protective monoclonal antibody, C3.1. The binding site of C3.1 binds short oligosaccharides of β1,2-linked mannopyranose residues present in the fungal cell wall phosphomannan. By delineating the fine detail of the molecular recognition of the cell wall β-mannan antigen, a disaccharide epitope was deduced to be the minimum size epitope that should induce the formation of protective antibody. Sequential functional group replacement of disaccharide hydroxyl groups to yield a series of monodeoxy and mono-O-methyl β1,2-linked mannobioside congeners established that three hydroxyl groups are essential for binding. Two of these, O-3 and O-4, are located on the internal mannose residue of the disaccharide, and a third, O-3', is located on the terminal mannose. Synthesis of a series of trisaccharides that mandate binding of either the reducing or nonreducing disaccharide epitopes provided the final indication that a disaccharide protein conjugate should have the potential to induce protective antibody. When disaccharide was conjugated to chicken serum albumin this vaccine produced antibodies in rabbits that recognized the native cell wall phosphomannan. In proof of concept protection experiments, three immunized rabbits showed a reduction in fungal burden when challenged with live C. albicans.

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“…As mentioned above, the OH by F substitution has been extensively used in carbohydrate chemistry to map the key hydroxyl groups of a given sugar that are involved in their recognition by lectins, antibodies, transporters, or enzymes. − The methodology presented herein, which employs a rationally assembled collection of monofluorinated monossaccharides for which their hydroxyl groups have been systematically substituted by fluorine atoms, allows dissecting chemical mapping information regarding the importance of each individual hydroxyl group in the interaction with its receptor. For MGL, the same experiment allows identifying its selectivity for Gal moieties and simultaneously shows that hydroxyls at positions 3 and 4 are essential to keep the interaction ability of the Gal analogue, while hydroxyls 2 and 6 can be modified while still maintaining binding to MGL.…”

Section: Discussionmentioning

confidence: 99%

“…From the molecular recognition perspective, different approaches have been tested to examine the relevance of hydroxyl groups from saccharide units in binding to receptors. One extensively applied approach rests on screening a given set of available closely related saccharides that display different stereochemistry and/or substitutions at a certain site within the sugar ring. − This protocol synthetically eliminates or modifies hydroxyl groups (deoxygenation, methylation, exchange by halogens) . In particular, hydroxyl-by-fluorine substitution has been used to trace key hydroxyl groups for contact with either lectins, antibodies, transporters, or enzymes …”

Section: Introductionmentioning

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Fluorinated Carbohydrates as Lectin Ligands: Simultaneous Screening of a Monosaccharide Library and Chemical Mapping by ¹⁹F NMR Spectroscopy

et al. 2020

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Molecular recognition of carbohydrates is a key step in essential biological processes. Carbohydrate receptors can distinguish monosaccharides even if they only differ in a single aspect of the orientation of the hydroxyl groups or harbor subtle chemical modifications. Hydroxyl-by-fluorine substitution has proven its merits for chemically mapping the importance of hydroxyl groups in carbohydrate–receptor interactions. 19 F NMR spectroscopy could thus be adapted to allow contact mapping together with screening in compound mixtures. Using a library of fluorinated glucose (Glc), mannose (Man), and galactose (Gal) derived by systematically exchanging every hydroxyl group by a fluorine atom, we developed a strategy combining chemical mapping and 19 F NMR T 2 filtering-based screening. By testing this strategy on the proof-of-principle level with a library of 13 fluorinated monosaccharides to a set of three carbohydrate receptors of diverse origin, i.e. the human macrophage galactose-type lectin, a plant lectin, Pisum sativum agglutinin, and the bacterial Gal-/Glc-binding protein from Escherichia coli , it became possible to simultaneously define their monosaccharide selectivity and identify the essential hydroxyls for interaction.

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Synthesis of monodeoxy and mono-O-methyl congeners of methyl β-d-mannopyranosyl-(1→2)-β-d-mannopyranoside for epitope mapping of anti-Candida albicans antibodies

Cited by 14 publications

References 23 publications

Chiral Phosphoric Acid Directed Regioselective Acetalization of Carbohydrate‐Derived 1,2‐Diols

Chiral Phosphoric Acid Directed Regioselective Acetalization of Carbohydrate‐Derived 1,2‐Diols

Design of a Candida albicans Disaccharide Conjugate Vaccine by Reverse Engineering a Protective Monoclonal Antibody

Fluorinated Carbohydrates as Lectin Ligands: Simultaneous Screening of a Monosaccharide Library and Chemical Mapping by ¹⁹F NMR Spectroscopy

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Synthesis of monodeoxy and mono-O-methyl congeners of methyl β-d-mannopyranosyl-(1→2)-β-d-mannopyranoside for epitope mapping of anti-Candida albicans antibodies

Cited by 14 publications

References 23 publications

Chiral Phosphoric Acid Directed Regioselective Acetalization of Carbohydrate‐Derived 1,2‐Diols

Chiral Phosphoric Acid Directed Regioselective Acetalization of Carbohydrate‐Derived 1,2‐Diols

Design of a Candida albicans Disaccharide Conjugate Vaccine by Reverse Engineering a Protective Monoclonal Antibody

Fluorinated Carbohydrates as Lectin Ligands: Simultaneous Screening of a Monosaccharide Library and Chemical Mapping by 19F NMR Spectroscopy

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Product

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Fluorinated Carbohydrates as Lectin Ligands: Simultaneous Screening of a Monosaccharide Library and Chemical Mapping by ¹⁹F NMR Spectroscopy