ANTIMICROBIAL ACTIVITIES OF AMPHIPHILIC PEPTIDES COVALENTLY BONDED TOA WATER-INSOLUBLE RESIN

A series of polymer-bound antimicrobial peptides was prepared, and the peptides were tested for their antimicrobial activities. The immobili zed peptides were prepared by a strategy that used solid-phase peptide synthesis that linked the carboxy-terminal amino acid with an ethylen ediamine-modified polyamide resin (PepsynK). The acid-stable, permanen t amide bond between the support and the nascent peptide renders the p eptide resistant to cleavage from the support during the final acid-ca talyzed deprotection step in the synthesis. Select immobilized peptide s containing amino acid sequences that ranged from the naturally occur ring magainin to simpler synthetic sequences with idealized secondary structures were excellent antimicrobial agents against several organis ms. The immobilized peptides typically reduced the number of viable ce lls by greater than or equal to 5 log units. We show that the reductio n in cell numbers cannot be explained by the action of a soluble compo nent. We observed no leached or hydrolyzed peptide from the resin, nor did we observe any antimicrobial activity in soluble extracts from th e immobilized peptide. The immobilized peptides were washed and reused for repeated microbial contact and killing. These results suggest tha t the surface actions by magainins and structurally related antimicrob ial peptides are sufficient for their lethal activities.