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.
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