Synthesis of PEGylated lactose analogs for inhibition studies on T.cruzi trans-sialidase

Trypanosoma cruzi, the agent of Chagas disease, expresses a unique enzyme, the trans-sialidase (TcTS) involved in the transfer of sialic acid from host glycoconjugates to mucins of the parasite. The enzyme is shed to the medium and may affect the immune system of the host. We have previously describ...

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Autores principales: Giorgi, M.E., Ratier, L., Agusti, R., Frasch, A.C.C., De Lederkremer, R.M.
Formato: JOUR
Materias:
Inhibitors
PEGylation
Trans-sialidase
Trypanosoma cruzi
benzyl beta dextro galactopyranosyl (1-6) 2 amino 2 deoxy alpha dextro glucopyranoside
glucopyranoside
lactobionolactone
lactose
lactose derivative
macrogol
sialidase inhibitor
unclassified drug
animal experiment
article
chemical modification
concentration response
controlled study
drug bioavailability
drug conjugation
drug stability
drug synthesis
enzyme inhibition
enzyme mechanism
mouse
nonhuman
priority journal
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_02820080_v27_n5_p549_Giorgi
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
id todo:paper_02820080_v27_n5_p549_Giorgi
record_format dspace
spelling todo:paper_02820080_v27_n5_p549_Giorgi2023-10-03T15:17:14Z Synthesis of PEGylated lactose analogs for inhibition studies on T.cruzi trans-sialidase Giorgi, M.E. Ratier, L. Agusti, R. Frasch, A.C.C. De Lederkremer, R.M. Inhibitors PEGylation Trans-sialidase Trypanosoma cruzi benzyl beta dextro galactopyranosyl (1-6) 2 amino 2 deoxy alpha dextro glucopyranoside glucopyranoside lactobionolactone lactose lactose derivative macrogol sialidase inhibitor unclassified drug animal experiment article chemical modification concentration response controlled study drug bioavailability drug conjugation drug stability drug synthesis enzyme inhibition enzyme mechanism mouse nonhuman priority journal Trypanosoma cruzi Trypanosoma cruzi Trypanosoma cruzi, the agent of Chagas disease, expresses a unique enzyme, the trans-sialidase (TcTS) involved in the transfer of sialic acid from host glycoconjugates to mucins of the parasite. The enzyme is shed to the medium and may affect the immune system of the host. We have previously described that lactose derivatives effectively inhibited the transfer of sialic acid to N-acetyllactosamine. Lactitol also prevented the apoptosis caused by the TcTS, although it is rapidly eliminated from the circulatory system. In this paper we report covalent conjugation of polyethylene glycol (PEG) with lactose, lactobionolactone and benzyl β-D-galactopyranosyl-(1→6)-2-amino-2- deoxy-α-D-glucopyranoside (1) with the hope to improve the bioavailability, though retaining their inhibitory properties. Different conjugation methods have been used and the behavior of the PEGylated products in the TcTS reaction was studied. © 2010 Springer Science+Business Media, LLC. Fil:Giorgi, M.E. 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:Agusti, R. 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. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_02820080_v27_n5_p549_Giorgi
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-134
collection Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic Inhibitors
PEGylation
Trans-sialidase
Trypanosoma cruzi
benzyl beta dextro galactopyranosyl (1-6) 2 amino 2 deoxy alpha dextro glucopyranoside
glucopyranoside
lactobionolactone
lactose
lactose derivative
macrogol
sialidase inhibitor
unclassified drug
animal experiment
article
chemical modification
concentration response
controlled study
drug bioavailability
drug conjugation
drug stability
drug synthesis
enzyme inhibition
enzyme mechanism
mouse
nonhuman
priority journal
Trypanosoma cruzi
Trypanosoma cruzi
spellingShingle Inhibitors
PEGylation
Trans-sialidase
Trypanosoma cruzi
benzyl beta dextro galactopyranosyl (1-6) 2 amino 2 deoxy alpha dextro glucopyranoside
glucopyranoside
lactobionolactone
lactose
lactose derivative
macrogol
sialidase inhibitor
unclassified drug
animal experiment
article
chemical modification
concentration response
controlled study
drug bioavailability
drug conjugation
drug stability
drug synthesis
enzyme inhibition
enzyme mechanism
mouse
nonhuman
priority journal
Trypanosoma cruzi
Trypanosoma cruzi
Giorgi, M.E.
Ratier, L.
Agusti, R.
Frasch, A.C.C.
De Lederkremer, R.M.
Synthesis of PEGylated lactose analogs for inhibition studies on T.cruzi trans-sialidase
topic_facet Inhibitors
PEGylation
Trans-sialidase
Trypanosoma cruzi
benzyl beta dextro galactopyranosyl (1-6) 2 amino 2 deoxy alpha dextro glucopyranoside
glucopyranoside
lactobionolactone
lactose
lactose derivative
macrogol
sialidase inhibitor
unclassified drug
animal experiment
article
chemical modification
concentration response
controlled study
drug bioavailability
drug conjugation
drug stability
drug synthesis
enzyme inhibition
enzyme mechanism
mouse
nonhuman
priority journal
Trypanosoma cruzi
Trypanosoma cruzi
description Trypanosoma cruzi, the agent of Chagas disease, expresses a unique enzyme, the trans-sialidase (TcTS) involved in the transfer of sialic acid from host glycoconjugates to mucins of the parasite. The enzyme is shed to the medium and may affect the immune system of the host. We have previously described that lactose derivatives effectively inhibited the transfer of sialic acid to N-acetyllactosamine. Lactitol also prevented the apoptosis caused by the TcTS, although it is rapidly eliminated from the circulatory system. In this paper we report covalent conjugation of polyethylene glycol (PEG) with lactose, lactobionolactone and benzyl β-D-galactopyranosyl-(1→6)-2-amino-2- deoxy-α-D-glucopyranoside (1) with the hope to improve the bioavailability, though retaining their inhibitory properties. Different conjugation methods have been used and the behavior of the PEGylated products in the TcTS reaction was studied. © 2010 Springer Science+Business Media, LLC.
format JOUR
author Giorgi, M.E.
Ratier, L.
Agusti, R.
Frasch, A.C.C.
De Lederkremer, R.M.
author_facet Giorgi, M.E.
Ratier, L.
Agusti, R.
Frasch, A.C.C.
De Lederkremer, R.M.
author_sort Giorgi, M.E.
title Synthesis of PEGylated lactose analogs for inhibition studies on T.cruzi trans-sialidase
title_short Synthesis of PEGylated lactose analogs for inhibition studies on T.cruzi trans-sialidase
title_full Synthesis of PEGylated lactose analogs for inhibition studies on T.cruzi trans-sialidase
title_fullStr Synthesis of PEGylated lactose analogs for inhibition studies on T.cruzi trans-sialidase
title_full_unstemmed Synthesis of PEGylated lactose analogs for inhibition studies on T.cruzi trans-sialidase
title_sort synthesis of pegylated lactose analogs for inhibition studies on t.cruzi trans-sialidase
url http://hdl.handle.net/20.500.12110/paper_02820080_v27_n5_p549_Giorgi
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AT ratierl synthesisofpegylatedlactoseanalogsforinhibitionstudiesontcruzitranssialidase
AT agustir synthesisofpegylatedlactoseanalogsforinhibitionstudiesontcruzitranssialidase
AT fraschacc synthesisofpegylatedlactoseanalogsforinhibitionstudiesontcruzitranssialidase
AT delederkremerrm synthesisofpegylatedlactoseanalogsforinhibitionstudiesontcruzitranssialidase
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