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.