An interdisciplinary investigation of antimicrobial peptides

Antimicrobial peptides (AMPs) have become a subject of research interest as a novel class of antimicrobial agents to complement conventional antibiotics. Because of their versatility and the low rate at which resistance against them develops, new research interest in them has been spurred. This study used an interdisciplinary approach to investigate the effect that the primary sequence of a short, cationic, alpha‐helical peptide has on antimicrobial activity. Computational and statistical methods were used to design peptide sequences that were complemented by experimental methods designed to assess antimicrobial activity. An analysis of data contained in two AMP databases (Antimicrobial Peptide Database (APD) and Collection of Anti‐Microbial Peptides (CAMP)) revealed that AMPs possess a number of factors in common that can explain their actions. Based on these factors, two test peptides were designed based on hydrophobic moment optimization and overall hydrophobicity, and tested for their ability to prevent bacterial cell growth, lyse red blood cells (RBCs), and liposomes. Software created for peptide structural analysis allowed for prediction of short AMP secondary structure through periodicity in the hydrophobicity as a function of the angle subtended. The experimentally tested peptides were both found to possess antimicrobial properties, but were also found to lyse RBCs and liposomes making them unfit for clinical use in their current state. However, the results of this study demonstrate that one can design short peptide sequences that mimic the actions of natural AMPs. With additional manipulation of specific properties, the primary sequence of the AMPs could be potentially tweaked to affect only microbes. This could open up a world of potential therapeutic agents useful in combating a host of microbial organisms, in particular multidrug‐resistant bacterial strains. Support or Funding Information F.W. & Elsie Heyl Foundation Summer Grant.