Synthesis and Thermodynamic Characterization of Small Cyclic Antimicrobial Arginine and Tryptophan-Rich Peptides with Selectivity for Gram-Negative Bacteria

Abstract

One promising strategy to combat the proliferation of bacteria resistance toward current antibiotics is the development of peptide-based drug. Among these compounds is a group of small cyclic peptides rich in arginine (Arg) and tryptophan (Trp) residues with selective toxicity toward Gram-negative bacteria. The small size of these peptides with improved toxicity toward Gram-negative bacteria makes them an interesting candidate to understand the forces responsible for their selectivity and paves the way to develop new therapeutics with potent activity toward multi-resistant Gram-negative bacteria. To reach this goal, isothermal titration calorimetry (ITC) is a useful technique which may provide the complete set of thermodynamic parameters of the interaction of peptides with lipid bilayers mimicking the properties of bacterial membranes within a few hours. The purpose of this chapter is to describe the synthesis of this group of small synthetic antimicrobial peptides together with the application of ITC to study their interaction with lipid membranes.