Insights into the Membranolytic Activity of Antimalarial Drug-Cell Penetrating Peptide Conjugates

• Type: Article in International Scientific Journal
• Date: 2021

Authors

Luísa Aguiar (Author) Other; Alexandra Maria F. R. Pinto (Author) FEUP; Ana Rute Neves (Author) Other; Nuno Vale (Author) FMUP; Sira Defaus (Author) Other; David Andreu (Author) Other; Salette Reis (Author) Other; Paula Gomes (Author) FCUP

Journal

Title: Membranes

Vol. 11 No. 1

Pages: 1-12

ISSN: 2077-0375

Publisher: MDPI

Indexing

ISI Web of Knowledge - 3 Citations

Scopus - 3 Citations

Other information

Authenticus ID: P-00T-6XF

DOI: 10.3390/membranes11010004

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12