Antimicrobial properties of the frog skin peptide, ranatuerin-1 and its [Lys-8]-substituted analog

Agnes Sonnevend, Floyd C. Knoop, Mahrendra Patel, Tibor Pál, Ana Maria Soto, J. Michael Conlon

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)


The predicted conformation of ranatuerin-1 (SMLSVLKNLG 10KVGLGFVACK20INK QC), an antimicrobial peptide first isolated from the skin of the bullfrog Rana catesbeiana, comprises three structural domains: α-helix (residues 1-8), β-sheet (residues 11-16) and β-turn (residues 20-25). Circular dichroism studies confirm significant α-helical character in 50% trifluoroethanol. Replacement of Cys-19 and Cys-25 by serine resulted only in decreased antimicrobial potency but deletion of either the cyclic heptapeptide region [residues (19-25)] or the N-terminal domain [residues (1-8)] produced inactive analogs. Substitution of the glycine residues in the central domain of the [Ser-19, Ser-25] analog by lysine produced inactive peptides despite increased α-helical content and cationicity. The substitution Asn-8→Lys gave a ranatuerin-1 analog with increased α-helicity and cationicity and increased potency against a range of Gram-positive and Gram-negative bacteria and against C. albicans but only a small increase (21%) in hemolytic activity. In contrast, increasing α-helicity and hydrophobicity by the substitution Asn-22→Ala resulted in a 3.5-fold increase in hemolytic activity. Effects on antimicrobial potencies of substitutions of neutral amino acids at positions 4, 18, 22, and 24 by lysine were less marked. Strains of pathogenic E. coli from different groups showed varying degrees of sensitivity to ranatuerin-1 (MIC between 5 and 40μM) but [Lys-8] ranatuerin-1 showed increased potency (between 2- and 8-fold; P<0.01) against all strains. The data demonstrate that [Lys-8] ranatuerin-1 shows potential as a candidate for drug development.

Original languageEnglish
Pages (from-to)29-36
Number of pages8
Issue number1
Publication statusPublished - Jan 2004
Externally publishedYes


  • Antimicrobial peptide
  • Drug development
  • Frog skin
  • Ranatuerin-1

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Endocrinology
  • Cellular and Molecular Neuroscience


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