Alanine Mutagenesis Identifies Specific Amino Acids of Nemertide Alpha-1 Activity and Its Binding to Target Receptors
Laborde, Q.; Peigneur, S.; Jacobsson, E.; Goransson, U.; Tytgat, J.; Andersson, H.S. (2026). Alanine Mutagenesis Identifies Specific Amino Acids of Nemertide Alpha-1 Activity and Its Binding to Target Receptors. J. Nat. Prod. 89(1): 95-103. https://dx.doi.org/10.1021/acs.jnatprod.5c01177
In: Journal of Natural Products. American Chemical Society/American Society of Pharmacognosy: Washington DC. ISSN 0163-3864; e-ISSN 1520-6025, more
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| Author keywords |
multiple sequence alignment;scorpion toxin;tris(2-carboxyethyl)phosphine;kappa |
| Authors | | Top |
- Laborde, Q.
- Peigneur, S., more
- Jacobsson, E.
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- Goransson, U.
- Tytgat, J.
- Andersson, H.S.
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| Abstract |
We recently discovered and characterized a novel family of peptide toxins, the alpha-nemertides, from the marine ribbon worm Lineus longissimus. These 31-residue peptides show potent neurotoxicity against invertebrate voltage-gated sodium (Nav) channels, making them promising candidates for biopesticide development. To explore structure-activity relationships, we synthesized 20 nemertide alpha-1 mutants (17 alanine, 3 lysine substitutions) to identify residues critical for activity and selectivity. Key positions, including S12, T17, N19, W22, and F24, were found to influence activity on Nav channels significantly. Notably, the S12A mutant showed high selectivity for invertebrate Navs, suggesting its potential as a selective tool or lead scaffold. Our findings highlight critical interaction points likely to be involved in binding to site 3 of domain IV on Nav channels and demonstrate how targeted modifications can sharpen selectivity. These insights support the rational design of more selective peptides and identify S12A as a promising candidate for further development as a biopesticide. |
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