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Coupling the antimalarial cell penetrating peptide TP10 to classical antimalarial drugs primaquine and chloroquine produces strongly hemolytic conjugates

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dc.contributor.author Aguiar, Luísa
dc.contributor.author Biosca, Arnau
dc.contributor.author Lantero, Elena
dc.contributor.author Gut, Jiri
dc.contributor.author Vale, Nuno
dc.contributor.author Rosenthal, Philip J.
dc.contributor.author Nogueira, Fátima
dc.contributor.author Andreu Martínez, David
dc.contributor.author Fernàndez Busquets, Xavier
dc.contributor.author Gomes, Paula
dc.date.accessioned 2020-01-10T08:39:15Z
dc.date.available 2020-01-10T08:39:15Z
dc.date.issued 2019
dc.identifier.citation Aguiar L, Biosca A, Lantero E, Gut J, Vale N, Rosenthal PJ, Nogueira F, Andreu D, Fernàndez-Busquets X, Gomes P. Coupling the antimalarial cell penetrating peptide TP10 to classical antimalarial drugs primaquine and chloroquine produces strongly hemolytic conjugates. Molecules. 2019; 24(24). pii: E4559. DOI 10.3390/molecules24244559
dc.identifier.issn 1420-3049
dc.identifier.uri http://hdl.handle.net/10230/43254
dc.description.abstract Recently, we disclosed primaquine cell penetrating peptide conjugates that were more potent than parent primaquine against liver stage Plasmodium parasites and non-toxic to hepatocytes. The same strategy was now applied to the blood-stage antimalarial chloroquine, using a wide set of peptides, including TP10, a cell penetrating peptide with intrinsic antiplasmodial activity. Chloroquine-TP10 conjugates displaying higher antiplasmodial activity than the parent TP10 peptide were identified, at the cost of an increased hemolytic activity, which was further confirmed for their primaquine analogues. Fluorescence microscopy and flow cytometry suggest that these drug-peptide conjugates strongly bind, and likely destroy, erythrocyte membranes. Taken together, the results herein reported put forward that coupling antimalarial aminoquinolines to cell penetrating peptides delivers hemolytic conjugates. Hence, despite their widely reported advantages as carriers for many different types of cargo, from small drugs to biomacromolecules, cell penetrating peptides seem unsuitable for safe intracellular delivery of antimalarial aminoquinolines due to hemolysis issues. This highlights the relevance of paying attention to hemolytic effects of cell penetrating peptide-drug conjugates.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher MDPI
dc.relation.ispartof Molecules. 2019; 24(24). pii: E4559
dc.rights © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.title Coupling the antimalarial cell penetrating peptide TP10 to classical antimalarial drugs primaquine and chloroquine produces strongly hemolytic conjugates
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.3390/molecules24244559
dc.subject.keyword Plasmodium
dc.subject.keyword Antimalarial
dc.subject.keyword Cell penetrating peptide
dc.subject.keyword Chloroquine
dc.subject.keyword Erythrocyte fluorescence
dc.subject.keyword Flow cytometry
dc.subject.keyword Hemolysis
dc.subject.keyword Microscopy
dc.subject.keyword Primaquine
dc.subject.keyword Red blood cell
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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