Skip to main content

IMIS

A new integrated search interface will become available in the next phase of marineinfo.org.
For the time being, please use IMIS to search available data

 

[ report an error in this record ]basket (0): add | show Print this page

Functional characterization of the nemertide α family of peptide toxins
Jacobsson, E.; Peigneur, S.; Andersson, H.S.; Laborde, Q.; Strand, M.; Tytgat, J.; Goransson, U. (2021). Functional characterization of the nemertide α family of peptide toxins. J. Nat. Prod. 84(8): 2121-2128. https://dx.doi.org/10.1021/acs.jnatprod.1c00104
In: Journal of Natural Products. American Chemical Society/American Society of Pharmacognosy: Washington DC. ISSN 0163-3864; e-ISSN 1520-6025, more
Peer reviewed article  

Available in  Authors 

Keyword
    Marine/Coastal

Authors  Top 
  • Jacobsson, E.
  • Peigneur, S., more
  • Andersson, H.S.
  • Laborde, Q.
  • Strand, M.
  • Tytgat, J., more
  • Goransson, U.

Abstract
    Peptide toxins find use in medicine, biotechnology, and agriculture. They are exploited as pharmaceutical tools, particularly for the investigation of ion channels. Here, we report the synthesis and activity of a novel family of peptide toxins: the cystine-knotted α nemertides. Following the prototypic α-1 and -2 (1 and 2), six more nemertides were discovered by mining of available nemertean transcriptomes. Here, we describe their synthesis using solid phase peptide chemistry and their oxidative folding by using an improved protocol. Nemertides α-2 to α-7 (2–7) were produced to characterize their effect on voltage-gated sodium channels (Blatella germanica BgNaV1 and mammalian NaVs1.1–1.8). In addition, ion channel activities were matched to in vivo tests using an Artemia microwell assay. Although nemertides demonstrate high sequence similarity, they display variability in activity on the tested NaVs. The nemertides are all highly toxic to Artemia, with EC50 values in the sub-low micromolar range, and all manifest preference for the insect BgNaV1 channel. Structure–activity relationship analysis revealed key residues for NaV-subtype selectivity. Combined with low EC50 values (e.g., NaV1.1: 7.9 nM (α-6); NaV1.3: 9.4 nM (α-5); NaV1.4: 14.6 nM (α-4)) this underscores the potential utility of α-nemertides for rational optimization to improve selectivity.

All data in the Integrated Marine Information System (IMIS) is subject to the VLIZ privacy policy Top | Authors