Antibacterial evaluation of structurally amphipathic, membrane active small cationic peptidomimetics: Synthesized by incorporating 3-amino benzoic acid as peptidomimetic element

• Synthesis of a series of 3-ABA based short cationic peptidomimetics.
• Lead peptidomimetics showed activity against MRSA & MRSE.
• Calcein dye leakage and fluorescent microscopy results display membrane disruption action on intact bacterial cells.
• Lead peptidomimetics were stable in plasma and even resistant pathogen (MRSA) was not able to develop resistance against them.

A new series of small cationic peptidomimetics were synthesized by incorporating 3-amino benzoic acid (3-ABA) in a small structural framework with the objective to mimic essential properties of natural antimicrobial peptides (AMPs). The new design approach resulted into improvement of activity and selectivity in comparison to linear peptides and allowed us to better understand the influence of structural amphipathicity on biological activity. Lead peptidomimetics displayed antibacterial activities against resistant pathogens (MRSA & MRSE). A calcein dye leakage experiment revealed a membranolytic effect of 4g and 4l which was further confirmed by fluorescence microscopy. In addition, proteolytic stability and no sign of resistance development against Staphylococcus aureus and MRSA demonstrate their potential for further development as novel antimicrobial therapeutics.

Newly designed small cationic peptidomimetics with potential antibacterial activity against antibiotic resistant pathogens (MRSA & MRSE).Figure optionsDownload as PowerPoint slide