Synthesis of β-galactosylamides as ligands of the peanut lectin. Insights into the recognition process

The synthesis of mono and divalent β-galactosylamides linked to a hydroxylated chain having a C2 symmetry axis derived from L-tartaric anhydride is reported. Reference compounds devoid of hydroxyl groups in the linker were also prepared from β-galactosylamine and succinic anhydride. After functional...

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Autores principales:	Varela, Oscar José, Kovensky, José Eduardo, Uhrig, María Laura
Publicado:	2017
Materias:	Divalent ligands ELLA assay Molecular dynamics Peanut agglutinin β-galactosylamides Binding energy Chains Chelation Ligands Oilseeds Proteins Scaffolds Azide-alkyne cycloaddition Binding affinities Functionalizations Lectin recognition Recognition process Reference compounds Succinic anhydride Copper compounds aglycone alkyne amide azide beta galactosylamide copper hydroxyl group lectin ligand succinic anhydride unclassified drug galactose peanut agglutinin protein binding Article catalysis controlled study cycloaddition enzymatic assay hydroxylation IC50 molecular docking molecular dynamics molecular recognition peanut priority journal synthesis chemistry metabolism molecular model protein conformation Galactose Models, Molecular Peanut Agglutinin Protein Binding Protein Conformation
Acceso en línea:	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00086215_v443-444_n_p58_Cano http://hdl.handle.net/20.500.12110/paper_00086215_v443-444_n_p58_Cano
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paper:paper_00086215_v443-444_n_p58_Cano
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spelling	paper:paper_00086215_v443-444_n_p58_Cano2023-06-08T14:33:06Z Synthesis of β-galactosylamides as ligands of the peanut lectin. Insights into the recognition process Varela, Oscar José Kovensky, José Eduardo Uhrig, María Laura Divalent ligands ELLA assay Molecular dynamics Peanut agglutinin β-galactosylamides Binding energy Chains Chelation Ligands Molecular dynamics Oilseeds Proteins Scaffolds Azide-alkyne cycloaddition Binding affinities Functionalizations Lectin recognition Peanut agglutinin Recognition process Reference compounds Succinic anhydride Copper compounds aglycone alkyne amide azide beta galactosylamide copper hydroxyl group lectin ligand succinic anhydride unclassified drug galactose ligand peanut agglutinin protein binding Article catalysis controlled study cycloaddition enzymatic assay hydroxylation IC50 molecular docking molecular dynamics molecular recognition peanut priority journal synthesis chemistry metabolism molecular model protein conformation Galactose Ligands Models, Molecular Peanut Agglutinin Protein Binding Protein Conformation The synthesis of mono and divalent β-galactosylamides linked to a hydroxylated chain having a C2 symmetry axis derived from L-tartaric anhydride is reported. Reference compounds devoid of hydroxyl groups in the linker were also prepared from β-galactosylamine and succinic anhydride. After functionalization with an alkynyl residue, the resulting building blocks were grafted onto different azide-equipped scaffolds through the copper catalyzed azide-alkyne cycloaddition. Thus, a family of structurally related mono and divalent β-N-galactopyranosylamides was obtained and fully characterized. The binding affinities of the ligands towards the model lectin PNA were measured by the enzyme-linked lectin assay (ELLA). The IC50 values were significantly higher than that of galactose but the presence of hydroxyl groups in the aglycone chain improved lectin recognition. Docking and molecular dynamics experiments were in accordance with the hypothesis that a hydroxyl group properly disposed in the linker could mimic the Glc O3 in the recognition process. On the other hand, divalent presentation of the ligands led to lectin affinity enhancements. © 2017 Elsevier Ltd Fil:Varela, O. 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. 2017 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00086215_v443-444_n_p58_Cano http://hdl.handle.net/20.500.12110/paper_00086215_v443-444_n_p58_Cano
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	Divalent ligands ELLA assay Molecular dynamics Peanut agglutinin β-galactosylamides Binding energy Chains Chelation Ligands Molecular dynamics Oilseeds Proteins Scaffolds Azide-alkyne cycloaddition Binding affinities Functionalizations Lectin recognition Peanut agglutinin Recognition process Reference compounds Succinic anhydride Copper compounds aglycone alkyne amide azide beta galactosylamide copper hydroxyl group lectin ligand succinic anhydride unclassified drug galactose ligand peanut agglutinin protein binding Article catalysis controlled study cycloaddition enzymatic assay hydroxylation IC50 molecular docking molecular dynamics molecular recognition peanut priority journal synthesis chemistry metabolism molecular model protein conformation Galactose Ligands Models, Molecular Peanut Agglutinin Protein Binding Protein Conformation
spellingShingle	Divalent ligands ELLA assay Molecular dynamics Peanut agglutinin β-galactosylamides Binding energy Chains Chelation Ligands Molecular dynamics Oilseeds Proteins Scaffolds Azide-alkyne cycloaddition Binding affinities Functionalizations Lectin recognition Peanut agglutinin Recognition process Reference compounds Succinic anhydride Copper compounds aglycone alkyne amide azide beta galactosylamide copper hydroxyl group lectin ligand succinic anhydride unclassified drug galactose ligand peanut agglutinin protein binding Article catalysis controlled study cycloaddition enzymatic assay hydroxylation IC50 molecular docking molecular dynamics molecular recognition peanut priority journal synthesis chemistry metabolism molecular model protein conformation Galactose Ligands Models, Molecular Peanut Agglutinin Protein Binding Protein Conformation Varela, Oscar José Kovensky, José Eduardo Uhrig, María Laura Synthesis of β-galactosylamides as ligands of the peanut lectin. Insights into the recognition process
topic_facet	Divalent ligands ELLA assay Molecular dynamics Peanut agglutinin β-galactosylamides Binding energy Chains Chelation Ligands Molecular dynamics Oilseeds Proteins Scaffolds Azide-alkyne cycloaddition Binding affinities Functionalizations Lectin recognition Peanut agglutinin Recognition process Reference compounds Succinic anhydride Copper compounds aglycone alkyne amide azide beta galactosylamide copper hydroxyl group lectin ligand succinic anhydride unclassified drug galactose ligand peanut agglutinin protein binding Article catalysis controlled study cycloaddition enzymatic assay hydroxylation IC50 molecular docking molecular dynamics molecular recognition peanut priority journal synthesis chemistry metabolism molecular model protein conformation Galactose Ligands Models, Molecular Peanut Agglutinin Protein Binding Protein Conformation
description	The synthesis of mono and divalent β-galactosylamides linked to a hydroxylated chain having a C2 symmetry axis derived from L-tartaric anhydride is reported. Reference compounds devoid of hydroxyl groups in the linker were also prepared from β-galactosylamine and succinic anhydride. After functionalization with an alkynyl residue, the resulting building blocks were grafted onto different azide-equipped scaffolds through the copper catalyzed azide-alkyne cycloaddition. Thus, a family of structurally related mono and divalent β-N-galactopyranosylamides was obtained and fully characterized. The binding affinities of the ligands towards the model lectin PNA were measured by the enzyme-linked lectin assay (ELLA). The IC50 values were significantly higher than that of galactose but the presence of hydroxyl groups in the aglycone chain improved lectin recognition. Docking and molecular dynamics experiments were in accordance with the hypothesis that a hydroxyl group properly disposed in the linker could mimic the Glc O3 in the recognition process. On the other hand, divalent presentation of the ligands led to lectin affinity enhancements. © 2017 Elsevier Ltd
author	Varela, Oscar José Kovensky, José Eduardo Uhrig, María Laura
author_facet	Varela, Oscar José Kovensky, José Eduardo Uhrig, María Laura
author_sort	Varela, Oscar José
title	Synthesis of β-galactosylamides as ligands of the peanut lectin. Insights into the recognition process
title_short	Synthesis of β-galactosylamides as ligands of the peanut lectin. Insights into the recognition process
title_full	Synthesis of β-galactosylamides as ligands of the peanut lectin. Insights into the recognition process
title_fullStr	Synthesis of β-galactosylamides as ligands of the peanut lectin. Insights into the recognition process
title_full_unstemmed	Synthesis of β-galactosylamides as ligands of the peanut lectin. Insights into the recognition process
title_sort	synthesis of β-galactosylamides as ligands of the peanut lectin. insights into the recognition process
publishDate	2017
url	https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00086215_v443-444_n_p58_Cano http://hdl.handle.net/20.500.12110/paper_00086215_v443-444_n_p58_Cano
work_keys_str_mv	AT varelaoscarjose synthesisofbgalactosylamidesasligandsofthepeanutlectininsightsintotherecognitionprocess AT kovenskyjoseeduardo synthesisofbgalactosylamidesasligandsofthepeanutlectininsightsintotherecognitionprocess AT uhrigmarialaura synthesisofbgalactosylamidesasligandsofthepeanutlectininsightsintotherecognitionprocess
_version_	1768544758324527104

Synthesis of β-galactosylamides as ligands of the peanut lectin. Insights into the recognition process

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