Synthesis and biological activity of ultra-short antimicrobial peptides bearing a novel non-coded amino acid

Aim SPPS & Peptides CharacterizationAntimicriobial resistance is a major concern for human health worldwide.Antimicrobial peptides and lipopeptides represent a promising alternative to conventional drugs in the fight against bacterial infections because of their ability to destroy cell membranes, causing damage difficult to fix, with a mechanism different from that of conventional antibiotics that act on specific targets.The major drawback in using peptides as drugs is their easy degradability by the enzymatic system of the human organism.The introduction of non-coded amino acids (NCAAs) should impart resistance to proteolysis.We focused on 2-amino-3-(1H-imidazol-1-yl)propanoic acid as the NCAA for our investigation, synthesizing both enantiomers in high yield and optical purity.Starting from known ultrashort antimicrobial peptides bearing a lipid moiety at the N-terminus [1], we designed and synthesized different analogs in which we inserted a new NCAA at different positions.We also investigated whether the insertion of the lipid chain at the C-terminus impacts the biologic activity of these compounds.(R)-and (S)-2-amino-3-(1H-imidazol-1-yl)propanoic acid (D-and L-His*)