Design and Synthesis of Novel Antimicrobial Peptoids

Abstract

Antimicrobial peptides (AMPs) are short, amphipathic cationic molecules. Tryptophan amino acid has been found to play an important role in protein folding and in altering the biological activities of peptides. Unlike conventional antibiotics, most AMPs act by lysing or disrupting the bacterial membrane. However, translation of AMPs to therapeutics has some limitations such as sensitivity to enzymatic degradation, low bioavailability, and high production cost. Oligo-N-substituted peptides (e.g. peptoids) are good alternatives to overcome the AMPs limitations. In this work, we designed and synthesized short peptoids containing the aromatic residues with cationic ammonium, guanidinium and quaternary ammonium groups. The effect of amino groups with different alkyl chains on antibacterial activity was investigated. Additionally, we examined the effect of an indole ring in the peptoids on their antibacterial and membrane-disruptive activities by comparing them with simple aromatic substituents. The antibacterial and hemolysis results of the synthesized compounds will also be presented.