Synthesis of divalent ligands of β-thio- And β-N-galactopyranosides and related lactosides and their evaluation as substrates and inhibitors of Trypanosoma cruzi trans-sialidase

In this work we describe the synthesis of mono- and divalent β-N - and β-S-galactopyranosides and related lactosides built on sugar scaffolds and their evaluation as substrates and inhibitors of the Trypanosoma cruzi trans-sialidase (TcTS). This enzyme catalyzes the transfer of sialic acid from an o...

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Detalles Bibliográficos
Publicado: 2014
Materias:
Multivalent ligands
Sialic acid
Sugar scaffolds
T. Cruzi trans-sialidase
β-galactopyranosides
Acceso en línea:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_18605397_v10_n_p3073_Cano
http://hdl.handle.net/20.500.12110/paper_18605397_v10_n_p3073_Cano
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
id paper:paper_18605397_v10_n_p3073_Cano
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spelling paper:paper_18605397_v10_n_p3073_Cano2023-06-08T16:29:26Z Synthesis of divalent ligands of β-thio- And β-N-galactopyranosides and related lactosides and their evaluation as substrates and inhibitors of Trypanosoma cruzi trans-sialidase Multivalent ligands Sialic acid Sugar scaffolds T. Cruzi trans-sialidase β-galactopyranosides In this work we describe the synthesis of mono- and divalent β-N - and β-S-galactopyranosides and related lactosides built on sugar scaffolds and their evaluation as substrates and inhibitors of the Trypanosoma cruzi trans-sialidase (TcTS). This enzyme catalyzes the transfer of sialic acid from an oligosaccharidic donor in the host, to parasite βGalp terminal units and it has been demonstrated that it plays an important role in the infection. Herein, the enzyme was also tested as a tool for the chemoenzymatic synthesis of sialic acid containing glycoclusters. The transfer reaction of sialic acid was performed using a recombinant TcTS and 3'-sialyllactose as sialic acid donor, in the presence of the acceptor having βGalp non reducing ends. The products were analyzed by high performance anion exchange chromatography with pulse amperometric detection (HPAEC-PAD). The ability of the different S-linked and N-linked glycosides to inhibit the sialic acid transfer reaction from 3'-sialyllactose to the natural substrate N-acetyllactosamine, was also studied. Most of the substrates behaved as good acceptors and moderate competitive inhibitors. A di-N -lactoside showed to be the strongest competitive inhibitor among the compounds tested (70% inhibition at equimolar concentration). The usefulness of the enzymatic trans-sialylation for the preparation of sialylated ligands was assessed by performing a preparative sialylation of a divalent substrate, which afforded the monosialylated compound as main product, together with the disialylated glycocluster. © 2014 Cano et al; licensee Beilstein-Institut. License and terms: see end of document. 2014 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_18605397_v10_n_p3073_Cano http://hdl.handle.net/20.500.12110/paper_18605397_v10_n_p3073_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 Multivalent ligands
Sialic acid
Sugar scaffolds
T. Cruzi trans-sialidase
β-galactopyranosides
spellingShingle Multivalent ligands
Sialic acid
Sugar scaffolds
T. Cruzi trans-sialidase
β-galactopyranosides
Synthesis of divalent ligands of β-thio- And β-N-galactopyranosides and related lactosides and their evaluation as substrates and inhibitors of Trypanosoma cruzi trans-sialidase
topic_facet Multivalent ligands
Sialic acid
Sugar scaffolds
T. Cruzi trans-sialidase
β-galactopyranosides
description In this work we describe the synthesis of mono- and divalent β-N - and β-S-galactopyranosides and related lactosides built on sugar scaffolds and their evaluation as substrates and inhibitors of the Trypanosoma cruzi trans-sialidase (TcTS). This enzyme catalyzes the transfer of sialic acid from an oligosaccharidic donor in the host, to parasite βGalp terminal units and it has been demonstrated that it plays an important role in the infection. Herein, the enzyme was also tested as a tool for the chemoenzymatic synthesis of sialic acid containing glycoclusters. The transfer reaction of sialic acid was performed using a recombinant TcTS and 3'-sialyllactose as sialic acid donor, in the presence of the acceptor having βGalp non reducing ends. The products were analyzed by high performance anion exchange chromatography with pulse amperometric detection (HPAEC-PAD). The ability of the different S-linked and N-linked glycosides to inhibit the sialic acid transfer reaction from 3'-sialyllactose to the natural substrate N-acetyllactosamine, was also studied. Most of the substrates behaved as good acceptors and moderate competitive inhibitors. A di-N -lactoside showed to be the strongest competitive inhibitor among the compounds tested (70% inhibition at equimolar concentration). The usefulness of the enzymatic trans-sialylation for the preparation of sialylated ligands was assessed by performing a preparative sialylation of a divalent substrate, which afforded the monosialylated compound as main product, together with the disialylated glycocluster. © 2014 Cano et al; licensee Beilstein-Institut. License and terms: see end of document.
title Synthesis of divalent ligands of β-thio- And β-N-galactopyranosides and related lactosides and their evaluation as substrates and inhibitors of Trypanosoma cruzi trans-sialidase
title_short Synthesis of divalent ligands of β-thio- And β-N-galactopyranosides and related lactosides and their evaluation as substrates and inhibitors of Trypanosoma cruzi trans-sialidase
title_full Synthesis of divalent ligands of β-thio- And β-N-galactopyranosides and related lactosides and their evaluation as substrates and inhibitors of Trypanosoma cruzi trans-sialidase
title_fullStr Synthesis of divalent ligands of β-thio- And β-N-galactopyranosides and related lactosides and their evaluation as substrates and inhibitors of Trypanosoma cruzi trans-sialidase
title_full_unstemmed Synthesis of divalent ligands of β-thio- And β-N-galactopyranosides and related lactosides and their evaluation as substrates and inhibitors of Trypanosoma cruzi trans-sialidase
title_sort synthesis of divalent ligands of β-thio- and β-n-galactopyranosides and related lactosides and their evaluation as substrates and inhibitors of trypanosoma cruzi trans-sialidase
publishDate 2014
url https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_18605397_v10_n_p3073_Cano
http://hdl.handle.net/20.500.12110/paper_18605397_v10_n_p3073_Cano
_version_ 1768543203409002496

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