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

Abstract

Dedicated to Professor Sambasivarao Kotha on the occasion of his 65th birthday.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 IC 50 , 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. 2055 (PDB ID: 3SRI) and performed short molecular dynamics (MD) simulations (two repeats of 30 ns). As two molecules of R1[a] Dr. J.

A conformationally constrained synthetic peptide efficiently inhibits malaria parasite entry into human red blood cells

“…22 However, till date, only a limited number of peptide/ mini-protein based inhibitors have been exploited to stop the interactions between P. falciparum proteins PfAMA1 and PfRON2. 17,[22][23][24][25][26][27] Several among those peptides are obtained using phage display [28][29][30][31][32] and several others are derived from the native 39-residue PfRON2 ectodomain. 18,20,26,33,34 The 39-residue polypeptide constitutes a small extracellular peptidic loop of the PfRON2 membrane protein that interacts with PfAMA1 very tightly during the moving junction formation.…”