Discovery of a Potent Conorfamide from Conus episcopatus Using a Novel Zebrafish Larvae Assay
| Autor: | Kevin Chase, Helena Safavi-Hemami, Joanna Gajewiak, Shrinivasan Raghuraman, Paula Flórez Salcedo, Cristoval Urcino, Randall T. Peterson, Baldomero M. Olivera, Samuel S. Espino, Maren Watkins, Sabrina Kozel, Gabriel D. Bossé, April Cabang |
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| Rok vydání: | 2021 |
| Předmět: |
Pharmacology
Conus episcopatus biology 010405 organic chemistry Bioactive molecules fungi Organic Chemistry Pharmaceutical Science Computational biology biology.organism_classification 01 natural sciences In vitro 0104 chemical sciences Analytical Chemistry Cone snail Conorfamide 010404 medicinal & biomolecular chemistry Complementary and alternative medicine In vivo Drug Discovery Zebrafish larvae Molecular Medicine Conotoxin |
| Zdroj: | Journal of Natural Products. 84:1232-1243 |
| ISSN: | 1520-6025 0163-3864 |
| DOI: | 10.1021/acs.jnatprod.0c01297 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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