Table 1. In Vitro Antiplasmodial Activity and Characteristics of PDIP Analogues.

^aSequence change relative to peptide 3, with the full amino acid sequence shown in Table S1; ds, disulfide bond.

^b% helicity was determined from the lowest MRE between 218 and 222 nm for 50 μM peptide in 100 mM NaF, 10 mM KH₂PO₄, pH 7.5 (Figures 4A, 5A, 6A).

^cRelative peptide binding PCPS/PC was determined using P/L at the end of the association phase of 16 μM peptide bound to POPC/POPS (4:1) compared to POPC bilayers (Figure 4C, 5C, 6C).

^d% peptide remaining was determined from area under the curve of the [M + 4]⁴⁺ peak (intact mass) using TOF-MS. Peptide analogues (50 μM) were incubated in 25% (v/v) serum in PBS at 37 °C for 24 h and compared to 0 h controls (100% peptide).

^ePf IC₅₀, peptide concentration to inhibit 50% growth of P. falciparum 3D7 compared to untreated controls, as determined from dose–response curves (Figure S5). Growth inhibition was determined from DAPI staining of parasite nuclei after 72 h incubation at 37 °C, 5% CO₂, 5% O₂. Culture medium was supplemented with either 5% serum, 2.5 mg/mL Albumax II (Ser + Alb), or 5 mg/mL Albumax II (Alb).

^fHemolysis HC₁₀, peptide concentration that lyses 10% of uninfected RBCs, determined from dose–response curves for released hemoglobin (Figure S6). Less than 10% hemolysis was confirmed within the active concentration range for 3, 10, 12, 24, and 26 up to 72 h incubation.

^gActivity-hemolysis index comparing 50% inhibition of in vitroP. falciparum (5 mg/mL Albumax II supplement) to 10% hemolysis of uninfected RBCs. Values highlighted in bold indicate improvements over the respective scaffold peptides (1–3).