Effects of deletion and insertion of amino acids on the activity of HelaTx1, a scorpion toxin on potassium channels. (1st March 2016)

• Record Type: Journal Article
• Authors: Peigneur, Steve; Esaki, Nao; Yamaguchi, Yoko; Tytgat, Jan; Sato, Kazuki
• Is Part Of: Toxicon. Volume 111(2016)
• Page Start: 1
• Page End: 5
• Publication Date: 2016-03-01
• Subjects: HelaTx1 -- Voltage-gated potassium channel -- Scorpion toxin -- Synthetic analog -- Amino acid deletion -- Amino acid insertion; CD circular dichroism -- Fmoc 9-fluorenylmethoxycarbonyl -- HefuTx1 κ-hefutoxin 1 -- MALDI-TOF-MS matrix assisted laser desorption/ionization time-of-flight mass spectrometry -- ODS octadecylsilane -- RP-HPLC reversed phase high performance liquid chromatography -- TFA trifluoroacetic acid; Toxins -- Periodicals; Venom -- Periodicals; 615.9
• DOI: 10.1016/j.toxicon.2015.12.014
• Languages: English
• ISSNs: 0041-0101

Abstract

Abstract: Four analogs of HelaTx1, a 25-mer peptide from scorpion venom, were synthesized by deleting its C-terminal hexapeptide fragment and N-terminal Ser residue and by inserting an amino acid in the middle part of the molecule. CD spectrum of HelaTx1(1–19) was almost superimposable to that of native HelaTx1. Functional characterization showed that HelaTx1(1–19) retained its inhibitory activity on Kv1.1 channel although 3 times less potent than HelaTx1, indicating that C-terminal part of HelaTx1 was not essential for its conformation and activity. Further deletion of N-terminal Ser residue and insertion of Ala in the middle part of the molecule affected the CD spectra and resulted in the decrease of activity. Highlights: Four analogs of HelaTx1 with deletion and insertion of amino acids were synthesized. HelaTx1 and HelaTx1(1–19) showed helical conformation. Deletion of C-terminal hexapeptide retained the activity of HelaTx1. Insertion of amino acid did not enhance the activity of HelaTx1.