Original Article

Amino Acids

, Volume 44, Issue 2, pp 645-660

First online:

Open Access This content is freely available online to anyone, anywhere at any time.

Effect of repetitive lysine–tryptophan motifs on the bactericidal activity of antimicrobial peptides

  • Ramamourthy GopalAffiliated withResearch Center for Proteineous Materials (RCPM), Chosun University
  • , Chang Ho SeoAffiliated withDepartment of Bioinformatics, Kongju National University
  • , Peter I. SongAffiliated withDepartment of Dermatology, University of Arkansas for Medical Sciences
  • , Yoonkyung ParkAffiliated withResearch Center for Proteineous Materials (RCPM), Chosun UniversityDepartment of Biotechnology, Chosun University Email author 


Previous studies identified lysine- and tryptophan-rich sequences within various cationic antimicrobial peptides. In the present study, we synthesized a series of peptides composed of lysine (K)-tryptophan (W) repeats (KW) n (where n equals 2, 3, 4 or 5) with amidation of the C-terminal to increase cationicity. We found that increases in chain length up to (KW)4 enhanced the peptides’ antibacterial activity; (KW)5 exhibited somewhat less bactericidal activity than (KW)4. Cytotoxicity, measured as lysis of human red blood cells, also increased with increasing chain length. With (KW)5, reduced antibacterial activity and increased cytotoxicity correlated with greater hydrophobicity and self-aggregation in the aqueous environment. The peptides acted by inducing rapid collapse of the bacterial transmembrane potential and induction of membrane permeability. The mode of interaction of the peptides and the phosphate groups of lipopolysaccharide was dependent upon the peptides’ ability to permeate the membrane. Longer peptides [(KW)4 and (KW)5] but not shorter peptides [(KW)2 and (KW)3] strongly bound and partially inserted into negatively charged, anionic lipid bilayers. These longer peptides also induced membrane permeabilization and aggregation of lipid vesicles. The peptides had a disordered structure in aqueous solution, and only (KW)4 and (KW)5 displayed a folded conformation on lipid membranes. Moreover, (KW)4 destroyed and agglutinated bacterial cells, demonstrating its potential as an antimicrobial agent. Collectively, the results show (KW)4 to be the most efficacious peptide in the (KW) n series, exhibiting strong antibacterial activity with little cytotoxicity.


Lysine Tryptophan Amidation Antimicrobial peptides Membrane permeabilization Bacterial agglutination