Peptide Antibiotics Developed by Mimicking Natural Antimicrobial Peptides Nihan Unubol 1,2* , Suleyman Selim Cinaroglu 3 , Merve Acikel Elmas 4 , Sümeyye Akçelik 3 , Arzu Tugba Ozal Ildeniz 5 , Serap Arbak 4 , Adil Allahverdiyev 1 and Tanil Kocagoz 2,3* 1 Department of Bioengineering, Faculty of Chemistry and Metallurgy, Yildiz Technical University, Istanbul, Turkey 2 Department of Medical Microbiology, School of Medicine, Acibadem University, Istanbul, Turkey 3 Department of Medical Biotechnology, Institute of Health Sciences, Acibadem University, Istanbul, Turkey 4 Department of Histology and Embryology, School of Medicine, Acibadem University, Istanbul, Turkey 5 Department of Medical Engineering, Faculty of Engineering, Acibadem University, Istanbul, Turkey * Corresponding author: Tanil Kocagoz, Department of Medical Microbiology, School of Medicine, Acibadem University, Istanbul, Turkey, Tel: +905323211784; E-mail: tanil.kocagoz@acibadem.edu.tr Nihan Unubol, Department of Medical Microbiology, School of Medicine, Acibadem University, Istanbul, Turkey, E-mail: nihan.unubol@acibadem.edu.tr Received date: July 07, 2017; Accepted date: August 3, 2017; Published date: August 7, 2017 Copyright: ©2017 Unubol N, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract 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. Keywords: Antimicrobial peptides; Peptide antibiotics; Cathelicidin Introduction Antimicrobial peptides (AMPs) are becoming a focus area for the emerging infectious diseases. Tey make up a large proportion of the natural immunity in a large group of organisms, from insects to humans. Tese are broad-spectrum antimicrobial peptides as a part of the cell-mediated immune system [1]. Most antimicrobial peptides (AMP) are stored in neutrophils and macrophage granules in animals and humans [2]. One of the most important common features of antimicrobial peptides is their amphophilic character, which is necessary for penetration into the membranes of pathogenic microorganisms. Additionally, the presence of negatively charged groups on bacterial membranes also creates electrostatic interaction with positively charged amphipathic groups of AMPs with the membranes. Te hydrophilic site in the structure of AMP enables the peptide to align correctly in a pathogenic membrane [3,4]. With the alteration of the secondary and tertiary structures of the cathelicidins changes the vertical orientation so that they are buried in the lipid bilayer and creates pores in the membrane. Te AMPs difusing into the outer membrane of Gram-negative bacteria can pass through the peptidoglycan layer and the inner membrane to the cytoplasm of the bacterial cell, respectively [5]. Although AMPs have common features, they have several diferent activities. Tese include immune- stimulation, antimicrobial activity and endotoxin neutralization [6]. Te main advantages of antimicrobial peptides are their broad- spectrum efciency, rapid action and low level of induced pathogen resistance. However, high costs of synthesis and susceptibility to proteases are their major disadvantages. Terefore, proteolytic susceptibility, pH sensitivity, their complex mode of action, decreased activity in physiological saline and serum and their production cost should be considered when developing AMPs to overcome their drawbacks [6-10]. Among AMPs, cathelicidins are members of a group of cationic peptides, a large group of molecules with amphipathic properties. Cathelicidins have a phylogenetically protected cathelin area [2]. Cathelicidins vary in amino acid sequence, and therefore in structure and size. Tey were frst found in mammalian bone marrow myeloid cells and later in epithelial cells. Cathelicidins have two functional domains that allow them to exhibit both interspecies and intraspecies diversity. Tese are the N-terminal Cathepsin L inhibitor site and the C-terminal antimicrobial domain [11-14]. Cathelicidins are positively charged peptides that electrostatically interact with microorganisms that have negatively charged cell membranes such as bacteria, fungi and parasites by forming transmembrane pores in the cell membrane and directly kill microorganisms. Additionally, they inhibit bacterial bioflm formation and act as antiviral agents [15-24]. Te cathelicidin mechanism of action, like other antimicrobial peptides, is in the form of disruption (damage and puncture) of cell membranes. Human cathelicidins do not act on healthy human cell membranes at physiological concentrations. It is suggested that the interaction of negatively charged lipid membranes with microorganisms and cationic Clinical Microbiology: Open Access Unubol et al., Clin Microbiol 2017, 6:4 DOI: 10.4172/2327-5073.1000291 Research Open Access Clin Microbiol, an open access journal ISSN:2327-5073 Volume 6 • Issue 4 • 1000291 C l i n i c a l M i c r o b i o l o g y : O p e n A c c es s ISSN: 2327-5073