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1.
Molecules ; 23(8)2018 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-30060568

RESUMEN

An efficient study of carbohydrate-protein interactions was achieved using multivalent glycodendrimer library. Different dendrimers with varied peripheral sugar densities and linkers provided an arsenal of potential novel therapeutic agents that could be useful for better specific action and greater binding affinities against their cognate protein receptors. Highly effective click chemistry represents the basic method used for the synthesis of mannosylated dendrimers. To this end, we used propargylated scaffolds of varying sugar densities ranging from 2 to 18 for the attachment of azido mannopyranoside derivatives using copper catalyzed click cycloaddition. Mannopyranosides with short and pegylated aglycones were used to evaluate their effects on the kinetics of binding. The mannosylated dendrons were built using varied scaffolds toward the accelerated and combined "onion peel" strategy These carbohydrates have been designed to fight E. coli urinary infections, by inhibiting the formation of bacterial biofilms, thus neutralizing the adhesion of FimH type 1 lectin present at the tip of their fimbriae against the natural multiantennary oligomannosides of uroplakin 1a receptors expressed on uroepithelial tissues. Preliminary DLS studies of the mannosylated dendrimers to cross- link the leguminous lectin Con A used as a model showed their high potency as candidates to fight the E. coli adhesion and biofilm formation.


Asunto(s)
Antibacterianos/síntesis química , Biopelículas/efectos de los fármacos , Dendrímeros/síntesis química , Lectinas/química , Manosa/química , Oligosacáridos/química , Adhesinas de Escherichia coli/genética , Adhesinas de Escherichia coli/metabolismo , Antibacterianos/metabolismo , Antibacterianos/farmacología , Azidas/química , Adhesión Bacteriana/efectos de los fármacos , Biopelículas/crecimiento & desarrollo , Química Clic , Concanavalina A/química , Concanavalina A/metabolismo , Reacción de Cicloadición , Dendrímeros/metabolismo , Dendrímeros/farmacología , Escherichia coli/efectos de los fármacos , Escherichia coli/crecimiento & desarrollo , Escherichia coli/metabolismo , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/microbiología , Proteínas Fimbrias/genética , Proteínas Fimbrias/metabolismo , Fimbrias Bacterianas/química , Fimbrias Bacterianas/efectos de los fármacos , Fimbrias Bacterianas/metabolismo , Expresión Génica , Glicosilación , Humanos , Lectinas/metabolismo , Modelos Biológicos , Polietilenglicoles/química , Infecciones Urinarias/tratamiento farmacológico , Infecciones Urinarias/microbiología , Uroplaquina Ia/genética , Uroplaquina Ia/metabolismo , Urotelio/efectos de los fármacos , Urotelio/metabolismo , Urotelio/microbiología
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