Abstract
A class of cationic antimicrobial peptides involved in host defense consists of sequences rich in Lys and Trp. Small peptides, (WK)~3~ and (KW)~3~, were designed by the combination of alternating Lys (K) and Trp (W) amino acids, and then their antimicrobial and hemolytic activities were determined. It was noticed that the reversed sequence of (KW)~3~ showed more activity against all strains than did (WK)~3~. The nonβhemolytic behavior of (WK)~3~ is identical to that of the reversed analog of (KW)~3~. CD spectra revealed that these peptides had an unfolded structure in buffer and EYPC:CH (10:1, w/w), but adopted folded conformation in the presence of EYPE:EYPG (7:3, w/w). The reversedβ(KW)~3~ peptide caused a higher extent of calcein release from EYPE:EYPG (7:3, w/w), though the activity was higher than that of the (WK)~3~. The interaction of the peptides with model lipid vesicles was examined using Trp fluorescence. The reversedβ(KW)~3~ showed higher interaction with EYPE:EYPG (7:3, w/w) membrane than did (WK)~3~. Both the peptides show less affinities while binding to EYPC:CH (10:1, w/w). This clearly indicated that the reversal of sequence factors is relevant to increased antimicrobial activity and lipid membrane permeability. Copyright Β© 2011 European Peptide Society and John Wiley & Sons, Ltd.