Glycoconjugate Journal

, Volume 27, Issue 5, pp 549–559 | Cite as

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

  • M. Eugenia Giorgi
  • Laura Ratier
  • Rosalía Agusti
  • Alberto C. C. Frasch
  • Rosa M. de Lederkremer
Article

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.

Keywords

Trans-sialidase PEGylation Inhibitors Trypanosoma cruzi 

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • M. Eugenia Giorgi
    • 1
  • Laura Ratier
    • 2
  • Rosalía Agusti
    • 1
  • Alberto C. C. Frasch
    • 2
  • Rosa M. de Lederkremer
    • 1
  1. 1.CIHIDECAR, Departamento de Química Orgánica, Facultad de Ciencias Exactas y NaturalesUniversidad de Buenos AiresBuenos AiresArgentina
  2. 2.Universidad Nacional de General San Martín y Consejo Nacional de Investigaciones Científicas y TécnicasGeneral San MartínArgentina

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