Synthesis and biological activity of divalent ligands based on 3-deoxy-4-thiolactose, an isosteric analogue of lactose
We report here the synthesis of divalent ligands containing 3-deoxy-4-thiolactose. This thiodisaccharide has been synthesized using the Michael addition of β-1-thiogalactose to the α,β-unsaturated system of sugar-derived dihydropyranones, followed by the reduction of the remaining carbonyl group. We...
| Publicado: |
2013
|
|---|---|
| Materias: | |
| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_14770520_v11_n33_p5500_Cagnoni http://hdl.handle.net/20.500.12110/paper_14770520_v11_n33_p5500_Cagnoni |
| Aporte de: |
| id |
paper:paper_14770520_v11_n33_p5500_Cagnoni |
|---|---|
| record_format |
dspace |
| spelling |
paper:paper_14770520_v11_n33_p5500_Cagnoni2023-06-08T16:18:03Z Synthesis and biological activity of divalent ligands based on 3-deoxy-4-thiolactose, an isosteric analogue of lactose Addition reactions Binding energy Bioactivity Chelation Escherichia coli Sugars Synthesis (chemical) Anomeric position Binding affinities High temperature Isothermal calorimetry Michael additions Micromolar range Peanut agglutinins (PNA) Recognition process Ligands Arachis hypogaea We report here the synthesis of divalent ligands containing 3-deoxy-4-thiolactose. This thiodisaccharide has been synthesized using the Michael addition of β-1-thiogalactose to the α,β-unsaturated system of sugar-derived dihydropyranones, followed by the reduction of the remaining carbonyl group. We were able to control the configuration (S) of the stereocenter linked to sulfur (C-4) of the reducing end by conducting the thioglycosylation at high temperature or by isomerization during the reduction of the 2-ulose thiodisaccharide with NaBH<inf>4</inf>/THF. The energy profile for this reaction on a model compound was calculated. The anomeric position of the 3-deoxy-4-thiolactose was functionalized with a terminal alkyne, which was coupled to azide-containing sugar scaffolds through CuAAC reaction to afford mono- and divalent ligands. The final products were competitive inhibitors of E. coli β-galactosidase in the micromolar range. Their binding affinities to peanut agglutinin (PNA) were determined by isothermal calorimetry, which showed a clear decrease in the K<inf>a</inf> values for monovalent derivatives compared to lactose. This report contributes to establishing the role of a particular hydroxyl group of lactose in sugar-protein recognition processes. © The Royal Society of Chemistry. 2013 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_14770520_v11_n33_p5500_Cagnoni http://hdl.handle.net/20.500.12110/paper_14770520_v11_n33_p5500_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 |
Addition reactions Binding energy Bioactivity Chelation Escherichia coli Sugars Synthesis (chemical) Anomeric position Binding affinities High temperature Isothermal calorimetry Michael additions Micromolar range Peanut agglutinins (PNA) Recognition process Ligands Arachis hypogaea |
| spellingShingle |
Addition reactions Binding energy Bioactivity Chelation Escherichia coli Sugars Synthesis (chemical) Anomeric position Binding affinities High temperature Isothermal calorimetry Michael additions Micromolar range Peanut agglutinins (PNA) Recognition process Ligands Arachis hypogaea Synthesis and biological activity of divalent ligands based on 3-deoxy-4-thiolactose, an isosteric analogue of lactose |
| topic_facet |
Addition reactions Binding energy Bioactivity Chelation Escherichia coli Sugars Synthesis (chemical) Anomeric position Binding affinities High temperature Isothermal calorimetry Michael additions Micromolar range Peanut agglutinins (PNA) Recognition process Ligands Arachis hypogaea |
| description |
We report here the synthesis of divalent ligands containing 3-deoxy-4-thiolactose. This thiodisaccharide has been synthesized using the Michael addition of β-1-thiogalactose to the α,β-unsaturated system of sugar-derived dihydropyranones, followed by the reduction of the remaining carbonyl group. We were able to control the configuration (S) of the stereocenter linked to sulfur (C-4) of the reducing end by conducting the thioglycosylation at high temperature or by isomerization during the reduction of the 2-ulose thiodisaccharide with NaBH<inf>4</inf>/THF. The energy profile for this reaction on a model compound was calculated. The anomeric position of the 3-deoxy-4-thiolactose was functionalized with a terminal alkyne, which was coupled to azide-containing sugar scaffolds through CuAAC reaction to afford mono- and divalent ligands. The final products were competitive inhibitors of E. coli β-galactosidase in the micromolar range. Their binding affinities to peanut agglutinin (PNA) were determined by isothermal calorimetry, which showed a clear decrease in the K<inf>a</inf> values for monovalent derivatives compared to lactose. This report contributes to establishing the role of a particular hydroxyl group of lactose in sugar-protein recognition processes. © The Royal Society of Chemistry. |
| title |
Synthesis and biological activity of divalent ligands based on 3-deoxy-4-thiolactose, an isosteric analogue of lactose |
| title_short |
Synthesis and biological activity of divalent ligands based on 3-deoxy-4-thiolactose, an isosteric analogue of lactose |
| title_full |
Synthesis and biological activity of divalent ligands based on 3-deoxy-4-thiolactose, an isosteric analogue of lactose |
| title_fullStr |
Synthesis and biological activity of divalent ligands based on 3-deoxy-4-thiolactose, an isosteric analogue of lactose |
| title_full_unstemmed |
Synthesis and biological activity of divalent ligands based on 3-deoxy-4-thiolactose, an isosteric analogue of lactose |
| title_sort |
synthesis and biological activity of divalent ligands based on 3-deoxy-4-thiolactose, an isosteric analogue of lactose |
| publishDate |
2013 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_14770520_v11_n33_p5500_Cagnoni http://hdl.handle.net/20.500.12110/paper_14770520_v11_n33_p5500_Cagnoni |
| _version_ |
1768544565287976960 |