Solid-phase synthesis of novel antimicrobial peptoids with α- and β-chiral side chains

Abstract

Bacterial resistance to conventional antibiotics poses an immense threat to human health and consequently many bacterial infections arise from multi-drug resistant pathogens. It is, therefore, necessary to continue to develop novel antimicrobials. Peptoids are a novel class of antimicrobial agents that mimic the structures of peptides. These N-substituted glycines differ from peptides in the side chain attachment site where in peptoids, the side chain functionality is introduced at the nitrogen rather than the α-carbon in peptides. During the process of design and development of antimicrobial peptoids, several key elements such as charge and amphiphilicity appear to guide peptoid bioactivity against bacterial pathogens. In this study, we report a quick synthesis of three novel cationic antimicrobial peptoids that contain charged, hydrophobic, and chiral monomers. This study is the first to use a monomer that contains both charge and chiral center for the design of the novel peptoid sequences.

Keywords: Amines; Antimicrobial peptoids; Chiral side chains; HPLC-MS; Peptoids; Resin; Solid-phase submonomer peptoid synthesis.