Length effects in antimicrobial peptides of the (RW)n series

Zhigang Liu, Anna Brady, Anne Young, Brian Rasimick, Kang Chen, Chunhui Zhou, Neville R. Kallenbach

Research output: Contribution to journalArticle

Abstract

A class of antimicrobial peptides involved in host defense consists of sequences rich in Arg and Trp-R and -W. Analysis of the pharmacophore in these peptides revealed that chains as short as trimers of sequences such as WRW and RWR have antimicrobial activity (M. B. Strom, B. E. Haug, M. L. Skar, W. Stensen, T. Stiberg, and J. S. Svendsen, J. Med. Chem. 46:1567-1570, 2003). To evaluate the effect of chain length on antimicrobial activity, we synthesized a series of peptides containing simple sequence repeats, (RW)n-NH 2 (where n equals 1, 2, 3, 4, or 5), and determined their antimicrobial and hemolytic activity. The antimicrobial activity of the peptides increases with chain length, as does the hemolysis of red blood cells. Within the experimental error, longer peptides (n equals 3, 4, or 5) show similar values for the ratio of hemolytic activity to antibacterial activity, or the hemolytic index. The (RW)3 represents the optimal chain length in terms of the efficacy of synthesis and selectivity as evaluated by the hemolytic index. Circular dichroism spectroscopy indicates that these short peptides appear to be unfolded in aqueous solution but acquire structure in the presence of phospholipids. Interaction of the peptides with model lipid vesicles was examined using tryptophan fluorescence. The (RW)n peptides preferentially interact with bilayers containing the negatively charged headgroup phosphatidylglycerol relative to those containing a zwitterionic headgroup, phosphatidylcholine.

Original languageEnglish (US)
Pages (from-to)597-603
Number of pages7
JournalAntimicrobial Agents and Chemotherapy
Volume51
Issue number2
DOIs
StatePublished - Feb 2007

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Peptides
Phosphatidylglycerols
Circular Dichroism
Hemolysis
Phosphatidylcholines
Tryptophan
Microsatellite Repeats
Phospholipids
Spectrum Analysis
Erythrocytes
Fluorescence
Lipids

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Liu, Z., Brady, A., Young, A., Rasimick, B., Chen, K., Zhou, C., & Kallenbach, N. R. (2007). Length effects in antimicrobial peptides of the (RW)n series. Antimicrobial Agents and Chemotherapy, 51(2), 597-603. https://doi.org/10.1128/AAC.00828-06

Length effects in antimicrobial peptides of the (RW)n series. / Liu, Zhigang; Brady, Anna; Young, Anne; Rasimick, Brian; Chen, Kang; Zhou, Chunhui; Kallenbach, Neville R.

In: Antimicrobial Agents and Chemotherapy, Vol. 51, No. 2, 02.2007, p. 597-603.

Research output: Contribution to journalArticle

Liu, Z, Brady, A, Young, A, Rasimick, B, Chen, K, Zhou, C & Kallenbach, NR 2007, 'Length effects in antimicrobial peptides of the (RW)n series', Antimicrobial Agents and Chemotherapy, vol. 51, no. 2, pp. 597-603. https://doi.org/10.1128/AAC.00828-06
Liu, Zhigang ; Brady, Anna ; Young, Anne ; Rasimick, Brian ; Chen, Kang ; Zhou, Chunhui ; Kallenbach, Neville R. / Length effects in antimicrobial peptides of the (RW)n series. In: Antimicrobial Agents and Chemotherapy. 2007 ; Vol. 51, No. 2. pp. 597-603.
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