Nihan Unubol, Suleyman Selim Cinaroglu, Merve Acikel Elmas, Sümeyye Akçelik, Arzu Tugba Ozal Ildeniz, Serap Arbak, Adil Allahverdiyev and Tanil Kocagoz
Antimicrobial peptides are widely preferred drugs for infectious disease treatment. Inspired from natural antimicrobial peptides, short peptides showing good antibacterial activity are designed in this study. The peptides consisted of repeating hydrophobic and positively charged amino acids, positioned on one side of the alpha helix. Arginine in peptides resulted in better activity compared to lysine. Having positively charged amino acids at both ends, created better activity for Escherichia coli compared to Staphylococcus aureus, and only at one end, created comparable activities for both organisms. Positioning of arginines on one side in zigzag form prominently increased the activity compared to positioning on linear axis. Elongating hydrophobic tail resulted in self-binding and eliminated the antibacterial activity. Molecular dynamic simulations suggested that a single molecule is capable of creating hydrophilic channel in membrane. Electron microscopic examination of staphylococci treated with these peptides revealed that the bacteria split into halves. Docking studies revealed that the peptides strongly bind to the major peptidoglycan synthesizing membrane protein, glycosyltransferase. The unique composition and design of these peptides revealed a promising antibacterial activity that may further lead to the development of new antimicrobial compounds effective to multi-drug resistant organisms.