Selective C-13-Labels on Repeating Glycan Oligomers to Reveal Protein Binding Epitopes through NMR: Polylactosamine Binding to Galectins

A combined chemo-enzymatic synthesis/NMR-based methodology is presented to identify, in unambiguous manner, the distinctive binding epitope within repeating sugar oligomers when binding to protein receptors. The concept is based on the incorporation of C-13-labels at specific monosaccharide units, s...

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Detalles Bibliográficos
Autores: Moure, María J., Gimeno, Ana, Delgado, Sandra, Diercks, Tammo, Boons, Geert-Jan, Jiménez Barbero, Jesús, Ardá, Ana
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/53528
Acceso en línea:http://hdl.handle.net/10810/53528
Access Level:acceso abierto
Palabra clave:galectins
molecular recognition
NMR
polylactosamine
selective C-13-labels
N-acetyllactosamine
ligand-binding
regulators
recognition
affinity
Descripción
Sumario:A combined chemo-enzymatic synthesis/NMR-based methodology is presented to identify, in unambiguous manner, the distinctive binding epitope within repeating sugar oligomers when binding to protein receptors. The concept is based on the incorporation of C-13-labels at specific monosaccharide units, selected within a repeating glycan oligomeric structure. No new chemical tags are added, and thus the chemical entity remains the same, while the presence of the C-13-labeled monosaccharide breaks the NMR chemical shift degeneracy that occurs in the non-labeled compound and allows the unique identification of the different components of the oligomer. The approach is demonstrated by a proof-of-concept study dealing with the interaction of a polylactosamine hexasaccharide with five different galectins that display distinct preferences for these entities.