Antimicrobial activity and mode of action of novel, N-terminal tagged tetra-peptidomimetics

We report herein, synthesis and mode of action of novel, cell selective, N-terminal tagged tetra-peptide conjugates. Analogues AP1 and AP2 with linoleic acid and p-terphenyl carboxylic acid tagging showed potent activity against Gram-positive and Gram-negative bacterial strains including the clinically relevant pathogen MRSA. For active analogues interaction studies with model bacterial mimic membranes revealed a direct correlation between activity and membrane perturbation. Further, active conjugates showed membrane depolarization and severe bacterial membrane disrupting ability. The hydrophobic-charge-hydrophobic template designed here can be useful in further optimizing end tagged peptidomimetics for therapeutic potential.