The presence of arginine in the Pro-Arg-Pro Motif augments the lethality of proline rich antimicrobial peptides of insect source

Abstract

Antimicrobial peptides are emerging as alternate drug candidates over couple of decades. The diversity exists in amino acid sequence, conformation and mechanism of action of these peptides. Cationic antimicrobial peptides constitute major class which is further classified depending on abundance of amino acid. Insect originated cationic proline rich antimicrobial peptides do not destabilize bacterial cell membrane but have intracellular targets. Some of the peptides belonging to proline rich class such as Apidaecins and Drosocin have unique tripeptide, Pro-Arg-Pro motif which is absent in Formaecin I of same group. Earlier we have designed a non-glycosylated analog of Formaecin I which contains a Pro-Lys-Pro motif. In this report, we have shown that substitution of lysine to arginine in Pro-Lys-Pro motif increases lethal action of this peptide against all the tested bacterial strains without affecting its structural, cytotoxic and membrane permeabilization properties. Importance of arginine in Pro-Arg- Pro motif is reemphasized when substitution of arginine to lysine in Pro-Arg-Pro, tripeptide sequence of Apidaecin and Drosocin results into decrease in their activity. Maintaining overall charge, this substitution indicates the role of arginine beyond providing cationicity