Insights into the membranolytic activity of antimalarial drug-cell penetrating peptide conjugates

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• dc.contributor.author Aguiar, Luísa
• dc.contributor.author Pinheiro, Marina
• dc.contributor.author Neves, Ana Rute
• dc.contributor.author Vale, Nuno
• dc.contributor.author Defaus, Sira
• dc.contributor.author Andreu Martínez, David
• dc.contributor.author Reis, Salette
• dc.contributor.author Gomes, Paula
• dc.date.accessioned 2021-02-16T07:02:11Z
• dc.date.available 2021-02-16T07:02:11Z
• dc.date.issued 2021
• dc.description.abstract Conjugation of TP10, a cell-penetrating peptide with intrinsic antimalarial activity, to the well-known antimalarial drugs chloroquine and primaquine has been previously shown to enhance the peptide's action against, respectively, blood- and liver-stage malaria parasites. Yet, this was achieved at the cost of a significant increase in haemolytic activity, as fluorescence microscopy and flow cytometry studies showed the conjugates to be more haemolytic for non-infected than for Plasmodium-infected red blood cells. To gain further insight into how these conjugates distinctively bind, and likely disrupt, membranes of both Plasmodium-infected and non-infected erythrocytes, we used dynamic light scattering and surface plasmon resonance to study the interactions of two representative conjugates and their parent compounds with lipid model membranes. Results obtained are herein reported and confirm that a strong membrane-disruptive character underlies the haemolytic properties of these conjugates, thus hampering their ability to exert selective antimalarial action.
• dc.format.mimetype application/pdf
• dc.identifier.citation Aguiar L, Pinheiro M, Neves AR, Vale N, Defaus S, Andreu D, Reis S, Gomes P. Insights into the membranolytic activity of antimalarial drug-cell penetrating peptide conjugates. Membranes (Basel). 2021; 11(1):4. DOI: 10.3390/membranes11010004
• dc.identifier.doi http://dx.doi.org/10.3390/membranes11010004
• dc.identifier.issn 2077-0375
• dc.identifier.uri http://hdl.handle.net/10230/46483
• dc.language.iso eng
• dc.publisher MDPI
• dc.relation.ispartof Membranes (Basel). 2020; 11(1):4
• dc.rights © 2020 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.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Antimalarial
• dc.subject.keyword Biophysics
• dc.subject.keyword Cell penetrating peptide
• dc.subject.keyword Dynamic light scattering
• dc.subject.keyword Haemolysis
• dc.subject.keyword Lipid membranes
• dc.subject.keyword Surface plasmon resonance
• dc.title Insights into the membranolytic activity of antimalarial drug-cell penetrating peptide conjugates
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion