Discovery of a Potent Conorfamide from Conus episcopatus Using a Novel Zebrafish Larvae Assay
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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Discovery of a Potent Conorfamide from Conus episcopatus Using a Novel Zebrafish Larvae Assay. / Bosse, Gabriel D; Urcino, Cristoval; Watkins, Maren; Flórez Salcedo, Paula; Kozel, Sabrina; Chase, Kevin; Cabang, April; Espino, Samuel S; Safavi-Hemami, Helena; Raghuraman, Shrinivasan; Olivera, Baldomero M; Peterson, Randall T; Gajewiak, Joanna.
I: Journal of Natural Products, Bind 84, Nr. 4, 2021, s. 1232-1243.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Discovery of a Potent Conorfamide from Conus episcopatus Using a Novel Zebrafish Larvae Assay
AU - Bosse, Gabriel D
AU - Urcino, Cristoval
AU - Watkins, Maren
AU - Flórez Salcedo, Paula
AU - Kozel, Sabrina
AU - Chase, Kevin
AU - Cabang, April
AU - Espino, Samuel S
AU - Safavi-Hemami, Helena
AU - Raghuraman, Shrinivasan
AU - Olivera, Baldomero M
AU - Peterson, Randall T
AU - Gajewiak, Joanna
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
U2 - 10.1021/acs.jnatprod.0c01297
DO - 10.1021/acs.jnatprod.0c01297
M3 - Journal article
C2 - 33764053
VL - 84
SP - 1232
EP - 1243
JO - Journal of Natural Products
JF - Journal of Natural Products
SN - 0163-3864
IS - 4
ER -
ID: 259041603