Identification of Plasmodium falciparum MSP‐1 peptides able to bind to human red blood cells

Abstract

To determine amino acid sequences of the Plasmodium falciparum MSP-1 protein that interact with red blood cell membranes in a specific receptor-ligand interaction, 78 sequential peptides, 20 amino acids long and spanning the entire length of the molecule, were synthesized and analysed with a specific binding assay developed for this purpose. Results show that peptides based on conserved and dimorphic regions of MSP-1, interact with human red blood cells (RBCs). This interaction occurs predominantly with peptides contained within the MSP-1 proteolytic fragments of 83 kDa, 38 kDa, 33 kDa and 19 kDa. Affinity constants of these peptides were between 140 and 250 nM. Peptide-RBC binding post enzyme treatment showed that the RBC receptors are not sialic acid dependent and appear to be proteic in nature. Some of these peptides inhibited merozoite invasion of RBCs yet did not inhibit intraerthrocytic development. These peptides, in conjunction with those from other merozoite surface proteins, may be used to rationally design a second generation of synthetic peptide-based malaria vaccines.

Band 3 is a host receptor binding merozoite surface protein 1 during thePlasmodium falciparuminvasion of erythrocytes

“…In contrast, it has been shown recently that a recombinant segment of MSP1 38 (p115MSP-1) binds to both wild-type and GPA-deficient En(aϪ) human RBCs (32). Further, short peptides derived from MSP1 83 , MSP1 38 , and MSP1 42 bound to sialic acid-depleted RBCs with relatively high affinity (33). To elucidate RBC binding properties of the MSP1 processing products, we carried out the binding assays shown in Fig.…”

Emerging Rules for Subunit-Based, Multiantigenic, Multistage Chemically Synthesized Vaccines

“…45 The same occurs with other conserved HABPs such as AMA-1-derived 4325 and MSP-derived 4044. The biological functions that have been determined for these native conserved HABPs (i.e., host cell binding ability [34][35][36][37][38][39][40] ) and immunological characteristics such as an immunological code of silence could thus be equal to or very similar to those presented by native proteins, strongly supporting our approach aimed at working with 15-25-mer, chemically synthesized peptides as a logical and rational methodology for minimal subunit-based synthetic vaccine development. FIGURE 2.…”

A GBP 130 derived peptide from Plasmodium falciparum binds to human erythrocytes and inhibits merozoite invasion in vitro

“…Radiolabeling -Peptides were labeled with 125 I by the chloramine T method (Urquiza et al 1996); 3.2 µl Na 125 I (17.2 mCi µg -1 ) was oxidized with 28 µg chloramine T and added to 5 µg of peptide. The reaction was stopped by addition of 14 µg sodium bisulfite in isotonic PBS (pH 7.4).…”

“…Screening assay -Increasing concentrations of radiolabeled peptide (16-100 nM) were added to a human erythrocyte suspension (3*10 8 cells), in the absence (total binding) or presence (non-specific binding) of unlabeled peptide (1.25 µM), and incubated for 1 h at room temperature (Urquiza et al 1996). After incubation, cells were washed five times with isotonic PBS.…”