# LaIT6: A Novel Insect-Selective K+-Channel Toxin from Liocheles australasiae Scorpion Venom

## TL;DR

A new insect-specific toxin from scorpion venom, LaIT6, was found to target potassium channels in insects without harming mammals.

## Contribution

LaIT6 is a novel insect-selective K+-channel toxin identified and chemically characterized from Liocheles australasiae scorpion venom.

## Key findings

- LaIT6 shows significant insecticidal activity against crickets without mammalian toxicity.
- Two basic and one aromatic residue in LaIT6's C-terminal region are crucial for its insecticidal activity.
- LaIT6 selectively inhibits insect K+ channels but not human ones, indicating species-specific selectivity.

## Abstract

Scorpion venom contains various insecticidal peptides. Previously, through transcriptome analysis of the venom gland of Liocheles australasiae, we identified precursor sequences of several peptides that share sequences similar to those acting on K+ channels. In this study, we chemically synthesized five of the peptides which were found in the venom and evaluated their insecticidal activity against crickets. This revealed that one of the peptides, named LaIT6, exhibited significant insecticidal activity without mammalian toxicity. To identify amino acid residues important for the insecticidal activity of LaIT6, nine analogs were synthesized mainly by substituting acidic, basic, and aromatic residues with alanine. This revealed that two basic residues and an aromatic residue in the C-terminal region are important for the activity. This characteristic of structure-activity relationships, known as a functional dyad, is commonly observed in peptides that act on K+ channels, suggesting that the action target of LaIT6 is K+ channels. As expected, LaIT6 showed significant inhibitory activity against insect K+ channels. Since no activity against human K+ channels was observed, we concluded that the selectivity of LaIT6 is determined by differences in the action on K+ channels between insects and mammals.