Title: Carbohydrate-binding non-peptidic pradimicins for the treatment of acute sleeping sickness in murine models
Authors: Castillo-Acosta, Víctor M
Ruiz-Pérez, Luis M
Etxebarria, Juan
Reichardt, Niels C
Navarro, Miguel
Igarashi, Yasuhiro
Liekens, Sandra
Balzarini, Jan
González-Pacanowska, Dolores # ×
Issue Date: Sep-2016
Publisher: Public Library of Science
Series Title: PLoS Pathogens vol:12 issue:9 pages:e1005851
Article number: 10.1371/journal.ppat.1005851
Abstract: Current treatments available for African sleeping sickness or human African trypanosomiasis (HAT) are limited, with poor efficacy and unacceptable safety profiles. Here, we report a new approach to address treatment of this disease based on the use of compounds that bind to parasite surface glycans leading to rapid killing of trypanosomes. Pradimicin and its derivatives are non-peptidic carbohydrate-binding agents that adhere to the carbohydrate moiety of the parasite surface glycoproteins inducing parasite lysis in vitro. Notably, pradimicin S has good pharmaceutical properties and enables cure of an acute form of the disease in mice. By inducing resistance in vitro we have established that the composition of the sugars attached to the variant surface glycoproteins are critical to the mode of action of pradimicins and play an important role in infectivity. The compounds identified represent a novel approach to develop drugs to treat HAT.
ISSN: 1553-7366
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Virology and Chemotherapy (Rega Institute)
× corresponding author
# (joint) last author

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