Aguiar Luísa, Pinheiro Marina, Neves Ana Rute, Vale Nuno, Defaus Sira, Andreu David, Reis Salette, Gomes Paula
LAQV-REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, Rua do Campo Alegre 687, P-4169-007 Porto, Portugal.
LAQV-REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira 228, P-4050-313 Porto, Portugal.
Membranes (Basel). 2020 Dec 22;11(1):4. doi: 10.3390/membranes11010004.
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 -infected red blood cells. To gain further insight into how these conjugates distinctively bind, and likely disrupt, membranes of both -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.
具有内在抗疟活性的细胞穿透肽TP10与著名的抗疟药物氯喹和伯氨喹缀合，此前已证明分别增强了该肽对血液期和肝期疟原虫的作用。然而，这是以溶血活性显著增加为代价实现的，因为荧光显微镜和流式细胞术研究表明，与未感染的红细胞相比，缀合物对未感染的红细胞更具溶血作用。为了进一步深入了解这些缀合物如何特异性结合并可能破坏感染和未感染红细胞的膜，我们使用动态光散射和表面等离子体共振来研究两种代表性缀合物及其母体化合物与脂质模型膜的相互作用。本文报告了所获得的结果，并证实这些缀合物的溶血特性具有很强的膜破坏特性，从而妨碍了它们发挥选择性抗疟作用的能力。
