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. 2024 Aug 1;10(8):2899–2912. doi: 10.1021/acsinfecdis.4c00276

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© 2024 The Authors. Published by American Chemical Society

Permits non-commercial access and re-use, provided that author attribution and integrity are maintained; but does not permit creation of adaptations or other derivative works (https://creativecommons.org/licenses/by-nc-nd/4.0/).

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First-generation PF4-derived internalization peptide (PDIP) analogue (cPF4PD, 1) targets and selectively enters RBCs infected with P. falciparum. (A) Normal uninfected RBCs (uRBC) have an asymmetric distribution of lipids, maintaining negatively charged phosphatidylserine (PS) headgroups on the inner leaflet of the cell plasma membrane, whereas PS is also present on the outer leaflet of infected RBCs (iRBC). Percentage RBC phospholipid data from ref (32). PC, phosphatidylcholine; SM, sphingomyelin; PE, phosphatidylethanolamine. (B) PDIP analogue (1) labeled with AlexaFluor-488 (A488) has rapid (<1 h) selective entry into iRBC and accumulates inside the parasite. Scale bars are 5 μm.