Lactose derivatives are inhibitors of Trypanosoma cruzi trans-sialidase activity toward conventional substrates in vitro and in vivo

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Chagas' disease, caused by Trypanosoma cruzi, affects about 18 million people in Latin America, and no effective treatment is available to date. To acquire sialic acid from the host glycoconjugates, T. cruzi expresses an unusual surface sialidase with trans-sialidase activity (TcTS) that transf...

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Autores principales:	Agustí, R., París, G., Ratier, L., Frasch, A.C.C., de Lederkremer, R.M.
Formato:	Artículo publishedVersion
Lenguaje:	Inglés
Publicado:	2004
Materias:	Alternative substrates HPAEC Inhibitors Trans-sialidase Trypanosoma cruzi 3 o beta dextro galactopyranosylarabinitol 3 o beta dextro galactopyranosylarabinofuranone 3 o beta dextro galactopyranosylarabinopyranose 5 (3' o beta dextro galactopyranosylglucopentitol 1' yl)tetrazole aminosugar carbohydrate derivative enzyme inhibitor lactitol lactobionic acid lactose lactose derivative n acetyllactosamine sialidase unclassified drug alkalinity amperometry anion exchange chromatography article binding site carbohydrate analysis concentration response controlled study drug efficacy drug structure enzyme activity enzyme inhibition enzyme specificity enzyme substrate human human cell in vitro study in vivo study parasite virulence priority journal Vero cell Animals Binding Sites Cercopithecus aethiops Chagas Disease Enzyme Inhibitors Glycoproteins Neuraminidase Protein Binding Protein Structure, Tertiary Sialic Acids Substrate Specificity Sugar Alcohols Vero Cells Virulence Mammalia Trypanosoma
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_09596658_v14_n7_p659_Agusti
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	paperaa:paper_09596658_v14_n7_p659_Agusti2023-06-12T16:48:43Z Lactose derivatives are inhibitors of Trypanosoma cruzi trans-sialidase activity toward conventional substrates in vitro and in vivo Glycobiology 2004;14(7):659-670 Agustí, R. París, G. Ratier, L. Frasch, A.C.C. de Lederkremer, R.M. Alternative substrates HPAEC Inhibitors Trans-sialidase Trypanosoma cruzi 3 o beta dextro galactopyranosylarabinitol 3 o beta dextro galactopyranosylarabinofuranone 3 o beta dextro galactopyranosylarabinopyranose 5 (3' o beta dextro galactopyranosylglucopentitol 1' yl)tetrazole aminosugar carbohydrate derivative enzyme inhibitor lactitol lactobionic acid lactose lactose derivative n acetyllactosamine sialidase unclassified drug alkalinity amperometry anion exchange chromatography article binding site carbohydrate analysis concentration response controlled study drug efficacy drug structure enzyme activity enzyme inhibition enzyme specificity enzyme substrate human human cell in vitro study in vivo study parasite virulence priority journal Trypanosoma cruzi Vero cell Animals Binding Sites Cercopithecus aethiops Chagas Disease Enzyme Inhibitors Glycoproteins Neuraminidase Protein Binding Protein Structure, Tertiary Sialic Acids Substrate Specificity Sugar Alcohols Trypanosoma cruzi Vero Cells Virulence Mammalia Trypanosoma Trypanosoma cruzi Chagas' disease, caused by Trypanosoma cruzi, affects about 18 million people in Latin America, and no effective treatment is available to date. To acquire sialic acid from the host glycoconjugates, T. cruzi expresses an unusual surface sialidase with trans-sialidase activity (TcTS) that transfers the sugar to parasite mucins. Surface sialic acid was shown to have relevant functions in protection of the parasite against the lysis by complement and in mammalian host cell invasion. The recently determined 3D structure of TcTS allowed a detailed analysis of its catalytic site and showed the presence of a lactose-binding site where the β-linked galactose accepting the sialic acid is placed. In this article, the acceptor substrate specificity of lactose derivatives was studied by high pH anion-exchange chromatography with pulse amperometric detection. The lactose open chain derivatives lactitol and lactobionic acid, as well as other derivatives, were found to be good acceptors of sialic acid. Lactitol, which was the best of the ones tested, effectively inhibited the transfer of sialic acid to N-acetyllactosamine. Furthermore, lactitol inhibited parasite mucins re-sialylation when incubated with live trypanosomes and TcTS. Lactitol also diminished the T. cruzi infection in cultured Vero cells by 20-27%. These results indicate that compounds directed to the lactose binding site might be good inhibitors of TcTS. © Oxford University Press 2004; all rights reserved. Fil:Agustí, R. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Ratier, L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:de Lederkremer, R.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2004 info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion application/pdf eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_09596658_v14_n7_p659_Agusti
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
language	Inglés
orig_language_str_mv	eng
topic	Alternative substrates HPAEC Inhibitors Trans-sialidase Trypanosoma cruzi 3 o beta dextro galactopyranosylarabinitol 3 o beta dextro galactopyranosylarabinofuranone 3 o beta dextro galactopyranosylarabinopyranose 5 (3' o beta dextro galactopyranosylglucopentitol 1' yl)tetrazole aminosugar carbohydrate derivative enzyme inhibitor lactitol lactobionic acid lactose lactose derivative n acetyllactosamine sialidase unclassified drug alkalinity amperometry anion exchange chromatography article binding site carbohydrate analysis concentration response controlled study drug efficacy drug structure enzyme activity enzyme inhibition enzyme specificity enzyme substrate human human cell in vitro study in vivo study parasite virulence priority journal Trypanosoma cruzi Vero cell Animals Binding Sites Cercopithecus aethiops Chagas Disease Enzyme Inhibitors Glycoproteins Neuraminidase Protein Binding Protein Structure, Tertiary Sialic Acids Substrate Specificity Sugar Alcohols Trypanosoma cruzi Vero Cells Virulence Mammalia Trypanosoma Trypanosoma cruzi
spellingShingle	Alternative substrates HPAEC Inhibitors Trans-sialidase Trypanosoma cruzi 3 o beta dextro galactopyranosylarabinitol 3 o beta dextro galactopyranosylarabinofuranone 3 o beta dextro galactopyranosylarabinopyranose 5 (3' o beta dextro galactopyranosylglucopentitol 1' yl)tetrazole aminosugar carbohydrate derivative enzyme inhibitor lactitol lactobionic acid lactose lactose derivative n acetyllactosamine sialidase unclassified drug alkalinity amperometry anion exchange chromatography article binding site carbohydrate analysis concentration response controlled study drug efficacy drug structure enzyme activity enzyme inhibition enzyme specificity enzyme substrate human human cell in vitro study in vivo study parasite virulence priority journal Trypanosoma cruzi Vero cell Animals Binding Sites Cercopithecus aethiops Chagas Disease Enzyme Inhibitors Glycoproteins Neuraminidase Protein Binding Protein Structure, Tertiary Sialic Acids Substrate Specificity Sugar Alcohols Trypanosoma cruzi Vero Cells Virulence Mammalia Trypanosoma Trypanosoma cruzi Agustí, R. París, G. Ratier, L. Frasch, A.C.C. de Lederkremer, R.M. Lactose derivatives are inhibitors of Trypanosoma cruzi trans-sialidase activity toward conventional substrates in vitro and in vivo
topic_facet	Alternative substrates HPAEC Inhibitors Trans-sialidase Trypanosoma cruzi 3 o beta dextro galactopyranosylarabinitol 3 o beta dextro galactopyranosylarabinofuranone 3 o beta dextro galactopyranosylarabinopyranose 5 (3' o beta dextro galactopyranosylglucopentitol 1' yl)tetrazole aminosugar carbohydrate derivative enzyme inhibitor lactitol lactobionic acid lactose lactose derivative n acetyllactosamine sialidase unclassified drug alkalinity amperometry anion exchange chromatography article binding site carbohydrate analysis concentration response controlled study drug efficacy drug structure enzyme activity enzyme inhibition enzyme specificity enzyme substrate human human cell in vitro study in vivo study parasite virulence priority journal Trypanosoma cruzi Vero cell Animals Binding Sites Cercopithecus aethiops Chagas Disease Enzyme Inhibitors Glycoproteins Neuraminidase Protein Binding Protein Structure, Tertiary Sialic Acids Substrate Specificity Sugar Alcohols Trypanosoma cruzi Vero Cells Virulence Mammalia Trypanosoma Trypanosoma cruzi
description	Chagas' disease, caused by Trypanosoma cruzi, affects about 18 million people in Latin America, and no effective treatment is available to date. To acquire sialic acid from the host glycoconjugates, T. cruzi expresses an unusual surface sialidase with trans-sialidase activity (TcTS) that transfers the sugar to parasite mucins. Surface sialic acid was shown to have relevant functions in protection of the parasite against the lysis by complement and in mammalian host cell invasion. The recently determined 3D structure of TcTS allowed a detailed analysis of its catalytic site and showed the presence of a lactose-binding site where the β-linked galactose accepting the sialic acid is placed. In this article, the acceptor substrate specificity of lactose derivatives was studied by high pH anion-exchange chromatography with pulse amperometric detection. The lactose open chain derivatives lactitol and lactobionic acid, as well as other derivatives, were found to be good acceptors of sialic acid. Lactitol, which was the best of the ones tested, effectively inhibited the transfer of sialic acid to N-acetyllactosamine. Furthermore, lactitol inhibited parasite mucins re-sialylation when incubated with live trypanosomes and TcTS. Lactitol also diminished the T. cruzi infection in cultured Vero cells by 20-27%. These results indicate that compounds directed to the lactose binding site might be good inhibitors of TcTS. © Oxford University Press 2004; all rights reserved.
format	Artículo Artículo publishedVersion
author	Agustí, R. París, G. Ratier, L. Frasch, A.C.C. de Lederkremer, R.M.
author_facet	Agustí, R. París, G. Ratier, L. Frasch, A.C.C. de Lederkremer, R.M.
author_sort	Agustí, R.
title	Lactose derivatives are inhibitors of Trypanosoma cruzi trans-sialidase activity toward conventional substrates in vitro and in vivo
title_short	Lactose derivatives are inhibitors of Trypanosoma cruzi trans-sialidase activity toward conventional substrates in vitro and in vivo
title_full	Lactose derivatives are inhibitors of Trypanosoma cruzi trans-sialidase activity toward conventional substrates in vitro and in vivo
title_fullStr	Lactose derivatives are inhibitors of Trypanosoma cruzi trans-sialidase activity toward conventional substrates in vitro and in vivo
title_full_unstemmed	Lactose derivatives are inhibitors of Trypanosoma cruzi trans-sialidase activity toward conventional substrates in vitro and in vivo
title_sort	lactose derivatives are inhibitors of trypanosoma cruzi trans-sialidase activity toward conventional substrates in vitro and in vivo
publishDate	2004
url	http://hdl.handle.net/20.500.12110/paper_09596658_v14_n7_p659_Agusti
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Lactose derivatives are inhibitors of Trypanosoma cruzi trans-sialidase activity toward conventional substrates in vitro and in vivo

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