Skip Navigation



Glycobiology Advance Access published online on April 7, 2004
Glycobiology, doi:10.1093/glycob/cwh079
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrow All Versions of this Article:
14/7/659    most recent
cwh079v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Agustí, R.
Right arrow Articles by de Lederkremer, R. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Agustí, R.
Right arrow Articles by de Lederkremer, R. M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Received February 6, 2004
Revised March 15, 2004
Accepted March 15, 2004

ORIGINAL ARTICLES

Lactose derivatives are inhibitors of Trypanosoma cruzi trans-sialidase activity towards conventional substrates in vitro and in vivo

Rosalía Agustí 1, Gastón París 2, Laura Ratier 2, Alberto C. C. Frasch 2, Rosa M. de Lederkremer 1*

1 CIHIDECAR, Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón II, 1428 Buenos Aires, Argentina
2 Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico de Chascomús, Universidad Nacional de General San Martín y Consejo Nacional de Investigaciones Cientificas y Tecnicas, INTI, Av. General Paz s/n, Edificio 24, Casilla de correo 30, 1650 General San Martín, Argentina

* To whom correspondence should be addressed. E-mail: lederk{at}qo.fcen.uba.ar.


  Abstract

Chagas' disease, caused by Trypanosoma cruzi, affects about 18 million people in Latin America and no effective treatment is available up to date. In order to acquire sialic acid from the host glycoconjugates, T. cruzi expresses an unusual surface sialidase with trans-sialidase activity (TcTS) that transfers the sugar to parasite mucins. Surface sialic acid was shown to have relevant functions in protection of the parasite against the lysis by complement, and in mammalian host cell invasion. The recently determined 3D structure of TcTS allowed a detailed analysis of its catalytic site and showed the presence of a lactose-binding site where the {beta}-linked galactose accepting the sialic acid is placed. In this work, the acceptor substrate specificity of lactose derivatives was studied by high pH anion-exchange chromatography with pulse amperometric detection. The lactose open chain derivatives lactitol and lactobionic acid, as well as other derivatives, were found to be good acceptors of sialic acid. Lactitol, which was the best of the ones tested, effectively inhibited the transfer of sialic acid to N-acetyllactosamine. Furthermore, lactitol inhibited parasite mucins re-sialylation when incubated with live trypanosomes and TcTS. Lactitol also diminished the T. cruzi infection in cultured Vero cells by 20-27%. These results indicate that compounds directed to the lactose binding site might be good inhibitors of TcTS.

Key words: alternative substrates, HPAEC, inhibitors, trans-sialidase, Trypanosoma cruzi


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 GlycobiologyHome page
R. M. de Lederkremer and A. C. C. Frasch
Letter to the Glyco-Forum: Relative efficacy of lactose-related donors for Trypanosoma cruzi trans-sialidase
Glycobiology, October 1, 2004; 14(10): 26G - 26G.
[Full Text]

Home page
 GlycobiologyHome page
J. O. Previato
Letter to the Glyco-Forum: {alpha}-2,3-Sialyllactitol is a donor substrate for Trypanosoma cruzi trans-sialidase
Glycobiology, October 1, 2004; 14(10): 25G - 25G.
[Full Text]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.