Synthesis and characterization of amino acid deletion analogs of κ-hefutoxin 1, a scorpion toxin on potassium channels

Toxicon. 2013 Sep;71:25-30. doi: 10.1016/j.toxicon.2013.05.010. Epub 2013 May 29.

Abstract

Nine analogs of scorpion toxin peptide κ-hefutoxin 1 were synthesized by stepwise deletion of its amino acid residues. Disulfide bond pairings of the synthetic analogs were confirmed by enzymatic digestion followed by MALDI-TOF-MS measurements. Functional characterization shows that analogs in which N-terminal residues were deleted retained biological activity, whereas deletion of middle part residues resulted in loss of activity. Furthermore, κ-hefutoxin 1 and analogs were subjected to a screening on voltage-gated potassium channels in order to determine their subtype selectivity. It is shown that κ-hefutoxin 1 is suitable as template for peptidomimetics in order to design small peptide-based therapeutic compounds.

Keywords: 9-fluorenylmethoxycarbonyl; Acm; Amino acid deletion; CD; Fmoc; Hef-1; MALDI-TOF-MS; ODS; RP-HPLC; Scorpion toxin; Subtype selectivity; Synthetic analogs; TFA; Trt; Voltage-gated potassium channel; acetamidomethyl; circular dichroism; matrix assisted laser desorption/ionization time-of-flight mass spectrometry; octadecylsilane; reversed phase high performance liquid chromatography; trifluoroacetic acid; triphenylmethyl; κ-Hefutoxin 1; κ-hefutoxin 1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Chemistry Techniques, Synthetic
  • Electrophysiological Phenomena
  • Molecular Sequence Data
  • Oocytes
  • Peptides / chemical synthesis
  • Peptides / chemistry
  • Potassium Channels, Voltage-Gated / antagonists & inhibitors*
  • Potassium Channels, Voltage-Gated / metabolism
  • Scorpion Venoms / chemical synthesis*
  • Scorpion Venoms / chemistry*
  • Scorpions / chemistry
  • Sequence Deletion
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Structure-Activity Relationship
  • Xenopus

Substances

  • Peptides
  • Potassium Channels, Voltage-Gated
  • Scorpion Venoms
  • kappa-hefutoxin 1, Heterometrus fulvipes