Serine repeat antigen peptides which bind specifically to red blood cells

Area of Science:

• Malariology
• Parasitology
• Molecular Biology

Background:

• Serine repeat antigen (SERA) is implicated in Plasmodium falciparum merozoite invasion of erythrocytes.
• Previous studies show SERA binding to erythrocyte membranes and inhibitory effects of antibodies and N-terminal fragments on invasion.

Purpose of the Study:

• To identify specific peptides within the SERA protein that bind to erythrocyte membranes.
• To characterize the binding properties and inhibitory potential of these SERA-derived peptides.

Main Methods:

• Synthesis and screening of 49 overlapping 20-residue peptides covering the FCR3 strain SERA protein.
• Quantification of binding affinity, binding sites, and Hill coefficients using competition assays.
• Assessment of inhibitory activity against merozoite invasion and intra-erythrocytic development.

Main Results:

• Seven SERA peptides demonstrated significant red blood cell (RBC) binding activity.
• Six high-binding peptides, located in conserved regions including the N-terminal domain, exhibited affinity constants between 150-1100 nM.
• Some identified peptides effectively inhibited in vitro merozoite invasion and parasite development within erythrocytes.

Conclusions:

• Specific SERA peptides possess erythrocyte binding capabilities crucial for Plasmodium falciparum invasion.
• These findings contribute to understanding the molecular mechanisms of red blood cell invasion by malaria parasites.
• Identified SERA peptides represent potential targets for novel antimalarial interventions.