title: Synthesis and characterization of amino acid deletion analogs of κ-hefutoxin 1, a scorpion toxin on potassium channels.
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.
authors.affiliation: Laboratory of Toxicology, University of Leuven-K.U. Leuven, Campus Gasthuisberg O&N2, Herestraat 49, P.O. Box 922, 3000 Leuven, Belgium.
authors.forename: Steve
authors.initials: S
authors.lastname: Peigneur
authors.forename: Yoko
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Hitomi
authors.initials: H
authors.lastname: Goto
authors.forename: Kellathur N
authors.initials: KN
authors.lastname: Srinivasan
authors.forename: Ponnampalam
authors.initials: P
authors.lastname: Gopalakrishnakone
authors.forename: Jan
authors.initials: J
authors.lastname: Tytgat
authors.forename: Kazuki
authors.initials: K
authors.lastname: Sato
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D060326:Chemistry Techniques, Synthetic; D055724:Electrophysiological Phenomena; D008969:Molecular Sequence Data; D009865:Oocytes; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012604:Scorpion Venoms / Q000138:chemical synthesis* / Q000737:chemistry*; D012605:Scorpions / Q000737:chemistry; D017384:Sequence Deletion; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013329:Structure-Activity Relationship; D014981:Xenopus
chemical_list: D010455:Peptides; D024642:Potassium Channels, Voltage-Gated; D012604:Scorpion Venoms; C586277:kappa-hefutoxin 1, Heterometrus fulvipes
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