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Abstract:

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.

Registro:

Documento: Artículo
Título:Synthesis of PEGylated lactose analogs for inhibition studies on T.cruzi trans-sialidase
Autor:Giorgi, M.E.; Ratier, L.; Agusti, R.; Frasch, A.C.C.; De Lederkremer, R.M.
Filiación:Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, 1428 Buenos Aires, Argentina
Universidad Nacional de General San Martín y Consejo Nacional, De Investigaciones Científicas y Técnicas, INTI, Av. General Paz 5445, 1650 General San Martín, Argentina
Palabras clave: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
Año:2010
Volumen:27
Número:5
Página de inicio:549
Página de fin:559
DOI: http://dx.doi.org/10.1007/s10719-010-9300-7
Título revista:Glycoconjugate Journal
Título revista abreviado:Glycoconjugate J.
ISSN:02820080
CODEN:GLJOE
CAS:lactose, 10039-26-6, 16984-38-6, 63-42-3, 64044-51-5; macrogol, 25322-68-3
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02820080_v27_n5_p549_Giorgi

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Citas:

---------- APA ----------
Giorgi, M.E., Ratier, L., Agusti, R., Frasch, A.C.C. & De Lederkremer, R.M. (2010) . Synthesis of PEGylated lactose analogs for inhibition studies on T.cruzi trans-sialidase. Glycoconjugate Journal, 27(5), 549-559.
http://dx.doi.org/10.1007/s10719-010-9300-7
---------- CHICAGO ----------
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" . Glycoconjugate Journal 27, no. 5 (2010) : 549-559.
http://dx.doi.org/10.1007/s10719-010-9300-7
---------- MLA ----------
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" . Glycoconjugate Journal, vol. 27, no. 5, 2010, pp. 549-559.
http://dx.doi.org/10.1007/s10719-010-9300-7
---------- VANCOUVER ----------
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. Glycoconjugate J. 2010;27(5):549-559.
http://dx.doi.org/10.1007/s10719-010-9300-7