Design and synthesis of hydrolytically stable multivalent ligands bearing thiodigalactoside analogues for peanut lectin and human galectin-3 binding

Herein, we describe the design and synthesis of a novel family of hydrolytically stable glycoclusters bearing thiodigalactoside (TDG) analogues as recognition elements of β-galactoside binding lectins. The TDG analogue was synthesized by thioglycosylation of a 6-S-acetyl-α-d-glucosyl bromide with th...

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Autores principales:	Cagnoni, Alejandro J., Kovensky, José Eduardo, Uhrig, María Laura
Publicado:	2014
Materias:	Amino acids Binding energy Bioactivity Escherichia coli Proteins Scaffolds Amino acid residues Binding affinities Copper(i) catalyzed azide alkyne cycloaddition (CuAAC) Isothermal titration calorimetry Microwave activation Multivalent effect Multivalent ligands Recognition element Ligands alkyne ascorbic acid azide beta galactoside bromine derivative copper sulfate cuprous ion galactoside galectin 3 ligand oligosaccharide peanut agglutinin triphenylphosphine galectin-3, human glycoconjugate lectin thiodigalactoside thioglycoside acetylation article binding affinity carbon nuclear magnetic resonance cycloaddition electrospray mass spectrometry glycosylation human hydrogen bond hydrolysis isothermal titration calorimetry microwave irradiation molecular docking molecular weight nonhuman nucleophilicity peanut protein binding proton nuclear magnetic resonance reaction time stoichiometry synthesis thin layer chromatography carbohydrate analysis chemical structure chemistry conformation molecular genetics Arachis hypogaea Carbohydrate Conformation Carbohydrate Sequence Galectin 3 Glycoconjugates Humans Hydrolysis Lectins Models, Molecular Molecular Sequence Data Thiogalactosides
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00223263_v79_n14_p6456_Cagnoni http://hdl.handle.net/20.500.12110/paper_00223263_v79_n14_p6456_Cagnoni
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	paper:paper_00223263_v79_n14_p6456_Cagnoni2023-06-08T14:49:37Z Design and synthesis of hydrolytically stable multivalent ligands bearing thiodigalactoside analogues for peanut lectin and human galectin-3 binding Cagnoni, Alejandro J. Kovensky, José Eduardo Uhrig, María Laura Amino acids Binding energy Bioactivity Escherichia coli Proteins Scaffolds Amino acid residues Binding affinities Copper(i) catalyzed azide alkyne cycloaddition (CuAAC) Isothermal titration calorimetry Microwave activation Multivalent effect Multivalent ligands Recognition element Ligands alkyne ascorbic acid azide beta galactoside bromine derivative copper sulfate cuprous ion galactoside galectin 3 ligand oligosaccharide peanut agglutinin triphenylphosphine galectin 3 galectin-3, human glycoconjugate lectin ligand thiodigalactoside thioglycoside acetylation article binding affinity carbon nuclear magnetic resonance cycloaddition electrospray mass spectrometry Escherichia coli glycosylation human hydrogen bond hydrolysis isothermal titration calorimetry microwave irradiation molecular docking molecular weight nonhuman nucleophilicity peanut protein binding proton nuclear magnetic resonance reaction time stoichiometry synthesis thin layer chromatography carbohydrate analysis chemical structure chemistry conformation molecular genetics peanut Arachis hypogaea Carbohydrate Conformation Carbohydrate Sequence Galectin 3 Glycoconjugates Humans Hydrolysis Lectins Ligands Models, Molecular Molecular Sequence Data Thiogalactosides Herein, we describe the design and synthesis of a novel family of hydrolytically stable glycoclusters bearing thiodigalactoside (TDG) analogues as recognition elements of β-galactoside binding lectins. The TDG analogue was synthesized by thioglycosylation of a 6-S-acetyl-α-d-glucosyl bromide with the isothiouronium salt of 2,3,4,6-tetra-O-acetyl-β-d-galactose. Further propargylation of the TDG analogue allowed the coupling to azido-functionalized oligosaccharide scaffolds through copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) under microwave activation. The final mono-, di-, and tetravalent ligands were resistant to enzymatic hydrolisis by Escherichia coli β-galactosidase. Binding affinities to peanut agglutinin and human galectin-3 were measured by isothermal titration calorimetry which showed Ka constants in the micromolar range as well as a multivalent effect. Monovalent ligand exhibited a binding affinity higher than that of thiodigalactoside. Docking studies performed with a model ligand on both β-galactoside binding lectins showed additional interactions between the triazole ring and lectin amino acid residues, suggesting a positive effect of this aromatic residue on the biological activity. © 2014 American Chemical Society. Fil:Cagnoni, A.J. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Kovensky, J. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Uhrig, M.L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2014 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00223263_v79_n14_p6456_Cagnoni http://hdl.handle.net/20.500.12110/paper_00223263_v79_n14_p6456_Cagnoni
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	Amino acids Binding energy Bioactivity Escherichia coli Proteins Scaffolds Amino acid residues Binding affinities Copper(i) catalyzed azide alkyne cycloaddition (CuAAC) Isothermal titration calorimetry Microwave activation Multivalent effect Multivalent ligands Recognition element Ligands alkyne ascorbic acid azide beta galactoside bromine derivative copper sulfate cuprous ion galactoside galectin 3 ligand oligosaccharide peanut agglutinin triphenylphosphine galectin 3 galectin-3, human glycoconjugate lectin ligand thiodigalactoside thioglycoside acetylation article binding affinity carbon nuclear magnetic resonance cycloaddition electrospray mass spectrometry Escherichia coli glycosylation human hydrogen bond hydrolysis isothermal titration calorimetry microwave irradiation molecular docking molecular weight nonhuman nucleophilicity peanut protein binding proton nuclear magnetic resonance reaction time stoichiometry synthesis thin layer chromatography carbohydrate analysis chemical structure chemistry conformation molecular genetics peanut Arachis hypogaea Carbohydrate Conformation Carbohydrate Sequence Galectin 3 Glycoconjugates Humans Hydrolysis Lectins Ligands Models, Molecular Molecular Sequence Data Thiogalactosides
spellingShingle	Amino acids Binding energy Bioactivity Escherichia coli Proteins Scaffolds Amino acid residues Binding affinities Copper(i) catalyzed azide alkyne cycloaddition (CuAAC) Isothermal titration calorimetry Microwave activation Multivalent effect Multivalent ligands Recognition element Ligands alkyne ascorbic acid azide beta galactoside bromine derivative copper sulfate cuprous ion galactoside galectin 3 ligand oligosaccharide peanut agglutinin triphenylphosphine galectin 3 galectin-3, human glycoconjugate lectin ligand thiodigalactoside thioglycoside acetylation article binding affinity carbon nuclear magnetic resonance cycloaddition electrospray mass spectrometry Escherichia coli glycosylation human hydrogen bond hydrolysis isothermal titration calorimetry microwave irradiation molecular docking molecular weight nonhuman nucleophilicity peanut protein binding proton nuclear magnetic resonance reaction time stoichiometry synthesis thin layer chromatography carbohydrate analysis chemical structure chemistry conformation molecular genetics peanut Arachis hypogaea Carbohydrate Conformation Carbohydrate Sequence Galectin 3 Glycoconjugates Humans Hydrolysis Lectins Ligands Models, Molecular Molecular Sequence Data Thiogalactosides Cagnoni, Alejandro J. Kovensky, José Eduardo Uhrig, María Laura Design and synthesis of hydrolytically stable multivalent ligands bearing thiodigalactoside analogues for peanut lectin and human galectin-3 binding
topic_facet	Amino acids Binding energy Bioactivity Escherichia coli Proteins Scaffolds Amino acid residues Binding affinities Copper(i) catalyzed azide alkyne cycloaddition (CuAAC) Isothermal titration calorimetry Microwave activation Multivalent effect Multivalent ligands Recognition element Ligands alkyne ascorbic acid azide beta galactoside bromine derivative copper sulfate cuprous ion galactoside galectin 3 ligand oligosaccharide peanut agglutinin triphenylphosphine galectin 3 galectin-3, human glycoconjugate lectin ligand thiodigalactoside thioglycoside acetylation article binding affinity carbon nuclear magnetic resonance cycloaddition electrospray mass spectrometry Escherichia coli glycosylation human hydrogen bond hydrolysis isothermal titration calorimetry microwave irradiation molecular docking molecular weight nonhuman nucleophilicity peanut protein binding proton nuclear magnetic resonance reaction time stoichiometry synthesis thin layer chromatography carbohydrate analysis chemical structure chemistry conformation molecular genetics peanut Arachis hypogaea Carbohydrate Conformation Carbohydrate Sequence Galectin 3 Glycoconjugates Humans Hydrolysis Lectins Ligands Models, Molecular Molecular Sequence Data Thiogalactosides
description	Herein, we describe the design and synthesis of a novel family of hydrolytically stable glycoclusters bearing thiodigalactoside (TDG) analogues as recognition elements of β-galactoside binding lectins. The TDG analogue was synthesized by thioglycosylation of a 6-S-acetyl-α-d-glucosyl bromide with the isothiouronium salt of 2,3,4,6-tetra-O-acetyl-β-d-galactose. Further propargylation of the TDG analogue allowed the coupling to azido-functionalized oligosaccharide scaffolds through copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) under microwave activation. The final mono-, di-, and tetravalent ligands were resistant to enzymatic hydrolisis by Escherichia coli β-galactosidase. Binding affinities to peanut agglutinin and human galectin-3 were measured by isothermal titration calorimetry which showed Ka constants in the micromolar range as well as a multivalent effect. Monovalent ligand exhibited a binding affinity higher than that of thiodigalactoside. Docking studies performed with a model ligand on both β-galactoside binding lectins showed additional interactions between the triazole ring and lectin amino acid residues, suggesting a positive effect of this aromatic residue on the biological activity. © 2014 American Chemical Society.
author	Cagnoni, Alejandro J. Kovensky, José Eduardo Uhrig, María Laura
author_facet	Cagnoni, Alejandro J. Kovensky, José Eduardo Uhrig, María Laura
author_sort	Cagnoni, Alejandro J.
title	Design and synthesis of hydrolytically stable multivalent ligands bearing thiodigalactoside analogues for peanut lectin and human galectin-3 binding
title_short	Design and synthesis of hydrolytically stable multivalent ligands bearing thiodigalactoside analogues for peanut lectin and human galectin-3 binding
title_full	Design and synthesis of hydrolytically stable multivalent ligands bearing thiodigalactoside analogues for peanut lectin and human galectin-3 binding
title_fullStr	Design and synthesis of hydrolytically stable multivalent ligands bearing thiodigalactoside analogues for peanut lectin and human galectin-3 binding
title_full_unstemmed	Design and synthesis of hydrolytically stable multivalent ligands bearing thiodigalactoside analogues for peanut lectin and human galectin-3 binding
title_sort	design and synthesis of hydrolytically stable multivalent ligands bearing thiodigalactoside analogues for peanut lectin and human galectin-3 binding
publishDate	2014
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00223263_v79_n14_p6456_Cagnoni http://hdl.handle.net/20.500.12110/paper_00223263_v79_n14_p6456_Cagnoni
work_keys_str_mv	AT cagnonialejandroj designandsynthesisofhydrolyticallystablemultivalentligandsbearingthiodigalactosideanaloguesforpeanutlectinandhumangalectin3binding AT kovenskyjoseeduardo designandsynthesisofhydrolyticallystablemultivalentligandsbearingthiodigalactosideanaloguesforpeanutlectinandhumangalectin3binding AT uhrigmarialaura designandsynthesisofhydrolyticallystablemultivalentligandsbearingthiodigalactosideanaloguesforpeanutlectinandhumangalectin3binding
_version_	1768545589489827840

Design and synthesis of hydrolytically stable multivalent ligands bearing thiodigalactoside analogues for peanut lectin and human galectin-3 binding

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