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Discovery of a potent conorfamide from Conus episcopatus using a novel zebrafish larvae assay
Bosse, G.D.; Urcino, C.; Watkins, M.; Flórez Salcedo, P.; Kozel, S.; Chase, K.; Cabang, A.; Espino, S.S.; Safavi-Hemami, H.; Raghuraman, S.; Olivera, B.M.; Peterson, R.T.; Gajewiak, J. (2021). Discovery of a potent conorfamide from Conus episcopatus using a novel zebrafish larvae assay. J. Nat. Prod. 84(4): 1232-1243. https://dx.doi.org/10.1021/acs.jnatprod.0c01297
In: Journal of Natural Products. American Chemical Society/American Society of Pharmacognosy: Washington DC. ISSN 0163-3864; e-ISSN 1520-6025
Peer reviewed article  
Beschikbaar in  Auteurs 
Trefwoorden
    Conus episcopatus da Motta, 1982 [WoRMS]
    Marien/Kust
Auteurs  Top 
  • Bosse, G.D.
  • Urcino, C.
  • Watkins, M.
  • Flórez Salcedo, P.
  • Kozel, S.
  • Chase, K.
  • Cabang, A.
  • Espino, S.S.
  • Safavi-Hemami, H.
  • Raghuraman, S.
  • Olivera, B.M.
  • Peterson, R.T.
  • Gajewiak, J.
Abstract
    Natural products such as conotoxins have tremendous potential as tools for biomedical research and for the treatment of different human diseases. Conotoxins are peptides present in the venoms of predatory cone snails that have a rich diversity of pharmacological functions. One of the major bottlenecks in natural products research is the rapid identification and evaluation of bioactive molecules. To overcome this limitation, we designed a set of light-induced behavioral assays in zebrafish larvae to screen for bioactive conotoxins. We used this screening approach to test several unique conotoxins derived from different cone snail clades and discovered that a conorfamide from Conus episcopatus, CNF-Ep1, had the most dramatic alterations in the locomotor behavior of zebrafish larvae. Interestingly, CNF-Ep1 is also bioactive in several mouse assay systems when tested in vitro and in vivo. Our novel screening platform can thus accelerate the identification of bioactive marine natural products, and the first compound discovered using this assay has intriguing properties that may uncover novel neuronal circuitry.
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