Isolation, Synthesis, and Pharmacological Characterization of a Short-Structured Peptide from the Venom of Phidippus Audax that Affects Potassium Currents

Posted by

 

Isolation, Synthesis, and Pharmacological Characterization of a Short-Structured Peptide from the Venom of Phidippus Audax that Affects Potassium Currents

Abstract

Purpose

Little is known about the venom of Salticidae spiders, so here, we look for venom peptides of the most cosmopolitan spider, Phidippus audax.

Methods

The isolation, chemical synthesis, and pharmacological characterization of a short peptide from the venom of the spider Phidippus audax (Araneae: Salticidae) was performed by HPLC chromatography, solid-phase peptide synthesis, and electrophysiology on rat dorsal root ganglia neurons, respectively.

Results

The unveiled peptide (Paudax1) consists of 22 residues and contains a single disulfide bridge. Paudax1 has paralytic activity against Acheta domesticus. It was synthesized in two N-terminal forms, Phi-Ala and Phi-Trp. . The pharmacology of both homologous peptides was evaluated in primary cultures of rat dorsal root ganglia neurons. Microperfusion of Phi-Ala [10 µM] (n = 6) resulted in a 17 ± 5% inhibition of the maximum amplitude of the outward current (p < 0.05) and a non-significant decrease of 22 ± 7% (p > 0.05) in the current amplitude at the end of the voltage pulse (IKend). Additionally, Phi-Ala did not affect the current inactivation time course (τinact). Meanwhile, the peptide Phi-Trp [10 µM] (n = 6) induced a 37 ± 3.6% inhibition (p ≤ 0.01) of the maximum amplitude of the outward current and a 44 ± 5% inhibition (p ≤ 0.01) in IKend, with no change in τinact.

Conclusion

Although both peptides, Phi-Ala and Phi-Trp, displayed insecticidal paralytic activity, they exhibited relatively low efficiency as blockers of the outward current at the concentrations used, and did not affect the inward currents. Phi-Trp and Phi-Ala are worth investigating to explore their therapeutic potential.

Salceda, E., Arenas, I., Olamendi-Portugal, T. et al. Isolation, Synthesis, and Pharmacological Characterization of a Short-Structured Peptide from the Venom of Phidippus Audax that Affects Potassium Currents. Int J Pept Res Ther 32, 15 (2026). https://doi.org/10.1007/s10989-025-10792-1