Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 1994 May;43(5):486-95.
doi: 10.1111/j.1399-3011.1994.tb00548.x.

Leiurotoxin I, a scorpion toxin specific for Ca(2+)-activated K+ channels. Structure-activity analysis using synthetic analogs

Affiliations

Leiurotoxin I, a scorpion toxin specific for Ca(2+)-activated K+ channels. Structure-activity analysis using synthetic analogs

J M Sabatier et al. Int J Pept Protein Res. 1994 May.

Abstract

Recently, we reported a structure-activity relationship study on P05, a novel leiurotoxin I-like scorpion toxin which is selective for the apamin-sensitive Ca(2+)-activated K+ channel [Sabatier et al. (1993) Biochemistry 32, 2763-2770]. Arg6, Arg7 and C-terminal His31 appeared to be key residues for P05 biological activity. Owing to the high sequence identity between P05 and leiurotoxin I (87%), several analogs of leiurotoxin I (Lei-NH2) with point mutations at these positions were designed and chemically synthesized using an optimized solid-phase technique. The synthesized peptides were [L6]Lei-NH2, [R7]Lei-NH2, Lei-OH and [R7]Lei-OH, as well as fragment [R7,Abu8]N4-S11-NH2. A chimeric analog ([M22,K24,R27]Lei-NH2), which possesses part of the iberiotoxin C-terminus, was also constructed. Circular dichroism analyses of these analogs, in agreement with their structural models obtained by molecular dynamics, showed that the point mutations did not significantly affect the overall secondary structures, as compared to natural Lei-NH2. All the peptides and natural toxins were compared in vitro for their capacity to inhibit binding of [125I]-apamin to rat brain synaptosomes, and in vivo for their specific neurotoxicity in mice. The Arg6 residue was essential for high biological activity of leiurotoxin I. Further, substitution of Met7 in the natural toxin by Arg7, or C-terminal amidation of His31, greatly increased affinity for the apamin receptor but did not significantly affect toxin neurotoxicity. Remarkably, the chimeric analog [M22,K24,R27]Lei-NH2 was found to retain leiurotoxin I-like activity, thus indicating that the negatively charged residues Asp24 and Glu27 (and Ile22) are not directly involved in the high toxin bioactivity. However, the chimeric molecule had no iberiotoxin-like effect on rat muscular maxi-K+ channels incorporated in lipid bilayers.

PubMed Disclaimer

MeSH terms

LinkOut - more resources