Efficient Synthesis of Thiolactoside Glycoclusters by Ruthenium-Catalyzed Cycloaddition Reaction of Disubstituted Alkynes on Carbohydrate Scaffolds

Lectin-carbohydrate interactions are responsible for several cellular processes involved in the immune system and the development of certain types of cancer. To further understanding of the cellular responses triggered by these interactions, complex carbohydrates are designed and prepared. Here, we...

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Detalles Bibliográficos
Autores: Cagnoni, Alejandro, Varela, Oscar Jose, Uhrig, Maria Laura, Kovensky, Jose Eduardo
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2013
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/17775
Acceso en línea:http://hdl.handle.net/11336/17775
Access Level:acceso abierto
Palabra clave:Carbohydrate
Glycoconjugate
Glycocluster
Click Reaction
Ruthenium
Calorimetry
https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
Descripción
Sumario:Lectin-carbohydrate interactions are responsible for several cellular processes involved in the immune system and the development of certain types of cancer. To further understanding of the cellular responses triggered by these interactions, complex carbohydrates are designed and prepared. Here, we describe the synthesis of a family of multivalent glycoclusters based on carbohydrate cores bearing thiolactosides or thiogalactosides as recognition elements with structural valencies ranging from 2 to 8. The synthetic strategy involves a key ruthenium-catalyzed cycloaddition reaction between symmetric disubstituted alkynes bearing two thiosugar units and azide-containing carbohydrate scaffolds. This methodology afforded high-valency glycoconjugates in good to excellent yields. Binding affinities of the synthetic β- thiolactosides for peanut lectin were measured by isothermal titration calorimetry. These titrations revealed micromolar affinities as well as a multivalent effect. A tetravalent glycoconjugate based on a trehalose scaffold displayed the highest binding affinity.