Mimicry of Antimicrobial Host-Defense Peptides

 

Top row: When designing a host-defense peptide (HDP) mimic, the most common approach involves designing a globally amphiphilic helix.  We show, with this nylon-3 polymer system (middle left), that a globally amphiphilic, irregular structure can also act as an effective HDP mimic.

Right: Activity as a function of percent cationic subunit (y) in polymers 3y.  For polymer 363, MHC/MIC = 32, demonstrating substantial selectivity for bacteria over eukaryotic cells.

Bottom left: Activity of polymer 360 compared to that of three widely-studied HDP and an artificial mutant known to be more active than natural magainin.1

 

 

1.  Mowery, B. P.; Lee, S. E.; Kissounko, D. A.; Epand, R. F.; Epand, R. M.; Weisblum, B.; Stahl, S. S.; Gellman, S. H. J. Am. Chem. Soc. 2007, 129, 15474.
2.  Epand, R. F.; Mowery, B. P.; Lee, S. E.; Stahl, S. S.; Lehrer, R. I.; Gellman, S. H.; Epand, R. M.  J. Mol. Biol. 2008, 371, 38.
3.  Mowery, B. P.; Dillon, A. H.; Weisblum, B.; Stahl, S. S.; Gellman, S.H. J. Am. Chem. Soc. 2009, 131, 9735.