A Chimeric Peptide Inhibits Red Blood Cell Invasion by Plasmodium falciparum with Hundredfold Increased Efficacy

Chembiochem. 2023 Apr 3;24(7):e202200533. doi: 10.1002/cbic.202200533. Epub 2022 Dec 23.

Abstract

Inhibiting the formation of a tight junction between two malaria parasite proteins, apical membrane antigen 1 and rhoptry neck protein 2, crucial for red blood cell invasion, prevents progression of the disease. In this work, we have used a unique approach to design a chimeric peptide, prepared by fusion of the best features of two peptide inhibitors, that has displayed parasite growth inhibition ex vivo with nanomolar IC50 , which is 100 times better than any of its parent peptides. Furthermore, to gain structural insights, we computationally modelled the hybrid peptide on its receptor.

Keywords: AMA1; MMPBSA; Plasmodium falciparum; peptide chimeras; peptides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Protozoan / chemistry
  • Antigens, Protozoan / metabolism
  • Erythrocytes / metabolism
  • Membrane Proteins / chemistry
  • Peptides / chemistry
  • Plasmodium falciparum* / metabolism
  • Protozoan Proteins* / metabolism

Substances

  • Protozoan Proteins
  • Antigens, Protozoan
  • Membrane Proteins
  • Peptides