Dimeric lipo-α/sulfono-γ-AA hybrid peptides as broad-spectrum antibiotic agents.

There is an urgent need to develop novel antibiotic agents that can combat emerging drug resistance. Herein, we report the design and investigation of a class of short dimeric antimicrobial lipo-α/sulfono-γ-AA hybrid peptides. Some of these peptides exhibit potent and broad-spectrum antimicrobial activity toward both clinically related Gram-positive and Gram-negative bacteria. The TEM study suggests that these hybrid peptides can compromise bacterial membranes and lead to bacterial death. Membrane depolarization and fluorescence microscopy studies also indicate that the mechanism of action is analogous to host-defense peptides (HDPs). Furthermore, the lead compound shows the ability to effectively inhibit biofilms formed from MRSA and E. coli. Further development of the short dimeric lipo-α/sulfono-γ-AA hybrid peptides may lead to a new generation of antimicrobial biomaterials to combat drug resistance.