Peptide toxins display many applications, including use in agriculture-, medicine and pharmacology. Some animals have successfully been investigated for peptide toxin presence, while others have been neglected. One neglected source of small peptide toxins is the epidermal mucus secreted by nemertean worms.
We have discovered and characterized a novel class of small cystine-rich neurotoxins, a-nemertides, in the mucus of the world’s longest animal: Lineus longissimus. The toxins could only be isolated in minute amounts and were sequenced using mass spectrometry in combination with transcriptomic data. The most abundant toxin, nemertide a-1, was synthetized by solid phase peptide synthesis in sufficient amounts for NMR-based structural elucidation and functional bioassays.
Upon injection, nemertide a-1 induces paralysis in Carcinus maenas at a concentration of 300 fmol/kg. In an Artemia salina assay, an IC50 of less than 1 µM was observed. Moreover, nemertide a-1 modulates voltage-gated sodium channels in insects at nM concentrations, while being approximately 100 times less active in vertebrates. These data indicate a potential use of a-nemertides in insecticidal applications.