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dc.contributor.author
Giorgi, María Eugenia
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Ratier, Laura
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Agusti, Rosalia
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Frasch, Alberto Carlos C.
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Muchnik, Rosa
dc.date.available
2019-01-16T20:17:38Z
dc.date.issued
2012-10
dc.identifier.citation
Giorgi, María Eugenia; Ratier, Laura; Agusti, Rosalia; Frasch, Alberto Carlos C.; Muchnik, Rosa; Improved bioavailability of inhibitors of Trypanosoma cruzi trans-sialidase: PEGylation of lactose analogs with multiarm polyethyleneglycol; Oxford Univ Press Inc; Glycobiology; 22; 10; 10-2012; 1363-1373
dc.identifier.issn
0959-6658
dc.identifier.uri
http://hdl.handle.net/11336/68166
dc.description.abstract
The trans-sialidase of Trypanosoma cruzi (TcTS) catalyzes the transfer of sialic acid from host glycoconjugates to terminal β-galactopyranosides in the mucins of the parasite. During infection, the enzyme is actively shed by the parasite to the bloodstream inducing hematological alterations. Lactitol prevents cell apoptosis caused by the TcTS, although it is rapidly eliminated from the circulatory system. Linear polyethyleneglycol (PEG) conjugates of lactose analogs were prepared but their clearance from blood was still quite fast. With the aim of improving their circulating half-lives in vivo, we now synthesized covalent conjugates of eight-arm PEG. The star-shape of these conjugates allows an increase in the molecular weight together with the loading of the active sugar. Two approaches were used for PEGylation of disaccharide derivatives containing β-d-Galp as the non-reducing unit. (1) Amide formation between benzyl-d-galactopyranosyl-(1→6)-2-amino-2-deoxy α-d-glucopyranoside and a succinimide-activated PEG. (2) Conjugation of lactobionolactone with amino end-functionalized PEG. Two 8-arm PEG derivatives (20 and 40 kDa) were used for each sugar. Substitution of all arms was proved by 1H nuclear magnetic resonance (NMR) spectroscopy. The bioavailability of the conjugates in mice plasma was considerably improved with respect to the 5 kDa linear PEG conjugates retaining their inhibitory properties.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Oxford Univ Press Inc
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Inhibitors
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Multiarm Conjugates
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Pegylation
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Trans-Sialidase
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Trypanosoma Cruzi
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Otras Ciencias Biológicas
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
Improved bioavailability of inhibitors of Trypanosoma cruzi trans-sialidase: PEGylation of lactose analogs with multiarm polyethyleneglycol
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2019-01-16T18:21:00Z
dc.journal.volume
22
dc.journal.number
10
dc.journal.pagination
1363-1373
dc.journal.pais
Reino Unido
dc.journal.ciudad
Oxford
dc.description.fil
Fil: Giorgi, María Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; Argentina
dc.description.fil
Fil: Ratier, Laura. Universidad Nacional de San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Agusti, Rosalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; Argentina
dc.description.fil
Fil: Frasch, Alberto Carlos C.. Universidad Nacional de San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Muchnik, Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Centro de Investigaciones en Hidratos de Carbono. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Centro de Investigaciones en Hidratos de Carbono; Argentina
dc.journal.title
Glycobiology
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://academic.oup.com/glycob/article/22/10/1363/1987859
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1093/glycob/cws091
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