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 journalArticle

14 Citations (Scopus)

Abstract

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 (US)
Pages (from-to)29-36
Number of pages8
JournalPeptides
Volume25
Issue number1
DOIs
StatePublished - Jan 1 2004

Fingerprint

Anura
Skin
Substitution reactions
Peptides
Rana catesbeiana
Lysine
Trifluoroethanol
Neutral Amino Acids
Hydrophobicity
Circular Dichroism
Gram-Negative Bacteria
Hydrophobic and Hydrophilic Interactions
Glycine
Serine
Escherichia coli
Conformations
Bacteria
ranatuerin
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Physiology
  • Biochemistry
  • Endocrinology
  • Cellular and Molecular Neuroscience

Cite this

Antimicrobial properties of the frog skin peptide, ranatuerin-1 and its [Lys-8]-substituted analog. / Sonnevend, Agnes; Knoop, Floyd C.; Patel, Mahrendra; Pál, Tibor; Soto, Ana Maria; Conlon, J. Michael.

In: Peptides, Vol. 25, No. 1, 01.01.2004, p. 29-36.

Research output: Contribution to journalArticle

Sonnevend, Agnes ; Knoop, Floyd C. ; Patel, Mahrendra ; Pál, Tibor ; Soto, Ana Maria ; Conlon, J. Michael. / Antimicrobial properties of the frog skin peptide, ranatuerin-1 and its [Lys-8]-substituted analog. In: Peptides. 2004 ; Vol. 25, No. 1. pp. 29-36.
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