title: Synthesis of PEGylated lactose analogs for inhibition studies on T.cruzi trans-sialidase.
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 beta-D-galactopyranosyl-(1-->6)-2-amino-2-deoxy-alpha-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.
authors.affiliation: CIHIDECAR, Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón II, 1428, Buenos Aires, Argentina.
authors.forename: M Eugenia
authors.initials: ME
authors.lastname: Giorgi
authors.forename: Laura
authors.initials: L
authors.lastname: Ratier
authors.forename: Rosalía
authors.initials: R
authors.lastname: Agusti
authors.forename: Alberto C C
authors.initials: AC
authors.lastname: Frasch
authors.forename: Rosa M
authors.initials: RM
authors.lastname: de Lederkremer
mesh_terms: D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D004187:Disaccharides / Q000737:chemistry*; D004337:Drug Carriers; D006023:Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007785:Lactose / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D008969:Molecular Sequence Data; D009077:Mucins / Q000378:metabolism; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D009439:Neuraminidase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011092:Polyethylene Glycols / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology*; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000201:enzymology*
chemical_list: D004187:Disaccharides; D004337:Drug Carriers; D006023:Glycoproteins; D009077:Mucins; D014344:Trypanocidal Agents; D011092:Polyethylene Glycols; C069715:trans-sialidase; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid; D007785:Lactose