Discovery of novel, neuronal cell-activating peptides in conotoxins

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Discovery of novel, neuronal cell-activating peptides in conotoxins

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Title: Discovery of novel, neuronal cell-activating peptides in conotoxins
Author/Creator: Reichhold, C | Vetter, I | Brooker, L R | Lewis, R J
Description: Cone sail venoms contain a vast array of bioactive peptides with a range of different properties, acting on membrane receptors and ion-channels. Conopeptides have evolved to be highly specific to their target with a high potency in the nano- and micromolar range. Many block voltage-gated ion-channels involved in the transmission of pain and conopeptides therefore represent valuable pharmaceutical targets. However, few peptides that act as activators on neuronal targets have been identified to date. This project concentrates on neuronal cell-activating conopeptides, as they are promising candidates for research tools, helping to understand the pharmacology and physiology of the targeted ionchannels and receptors. We have investigated the venom of nine different Conus species (Conus litteratus, C. capitaneus, C. eburneus, C. catus, C. chaldeus, C. miliaris, C. pulicarius, C. aristophanes, C. leaopardus). To guide discovery of novel activating peptides, a high-throughput Ca2+ imaging platform (FLIPR) was used in conjunction with reverse-phase high pressure liquid chromatography (RP-HPLC). Activity of cone snail venom was tested on human neuroblastoma cell lines, selected according to their expression of ion-channels and receptors involved in the pain pathway. Activity was found in seven of the nine tested crude Conus venoms. However, isolated peptides could not be recovered after fractionation, suggesting synergistic effects of peptides and non-peptide compounds. The latter will be identified and further investigations will be expanded to other venomous species. Once novel neuronal cell-activating peptides are identified and sequenced, they will be synthesized and structurally and biologically characterised using high-content imaging, electrophysiology and mutational scans.
Relation: 2010 ComBio Conference, Christchurch, New Zealand 6-10 December 2009
Relation: http://www.canterbury.ac.nz/conference/combio09/
Year: 2009
Publisher: Australian Society for Biochemistry and Molecular Biology
Subject: FoR 0601 (Biochemistry and Cell Biology) | conotoxins | cone snails

Resource Type: Conference Poster

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