Analysis of a cone snail's killer cocktail – The milked venom of Conus geographus

Bingham, Jon Paul; Baker, Margaret R.; Chun, Joycelyn B.

doi:10.1016/j.toxicon.2012.07.014

Cited by 20 publications

(7 citation statements)

References 11 publications

(11 reference statements)

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“…1). All chromatograms display complex compositions and excellent resolution that compares to previously reported RP-HPLC profiles of injected venom from C. purpurascens [21,27] and other fish-hunting Conus species (C. geographus [28], C. consors [12], C. striatus [16], and C. ermineus [20]). There were between 97 and 150 fractions manually collected from the injected venom sample of each specimen.…”

Section: Rp-hplc Chromatographic Profiles Of Injected Venom and Maldisupporting

confidence: 51%

Intraspecific variations in Conus purpurascens injected venom using LC/MALDI-TOF-MS and LC-ESI-TripleTOF-MS

et al. 2015

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The venom of cone snails is composed of highly modified peptides (conopeptides) that target a variety of ion channels and receptors. The venom of these marine gastropods represents a largely untapped resource of bioactive compounds of potential pharmaceutical value. Here, we use a combination of bioanalytical techniques to uncover the extent of venom expression variability in Conus purpurascens, a fish-hunting cone snail species. The injected venom of nine specimens of C. purpurascens was separated by reversed-phase high-performance liquid chromatography (RP-HPLC), and fractions were analyzed using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS) in parallel with liquid chromatography-electrospray ionization (LC-ESI)-TripleTOF-MS to compare standard analytical protocols used in preparative bioassay-guided fractionations with a deeper peptidomic analysis. Here, we show that C. purpurascens exhibits pronounced intraspecific venom variability. RP-HPLC fractionation followed by MALDI-TOF-MS analysis of the injected venom of these nine specimens identified 463 distinct masses, with none common to all specimens. Using LC-ESI-TripleTOF-MS, the injected venom of these nine specimens yielded a total of 5517 unique masses. We also compare the injected venom of two specimens with their corresponding dissected venom. We found 2566 and 1990 unique masses for the dissected venom compared to 941 and 1959 masses in their corresponding injected venom. Of these, 742 and 1004 masses overlapped between the dissected and injected venom, respectively. The results indicate that larger conopeptide libraries can be assessed by studying multiple individuals of a given cone snail species. This expanded library of conopeptides enhances the opportunities for discovery of molecular modulators with direct relevance to human therapeutics. Graphical Abstract The venom of cone snails are extraordinarily complex mixtures of highly modified peptides. Venom analysis requires separation through RP-HPLC followed by MALDI-TOF mass spectrometry or direct analysis using LC-ESI-TripleTOF-MS. Using these techniques, venom intraspecific variability and comparison between injected and dissected were assessed.

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Section: Rp-hplc Chromatographic Profiles Of Injected Venom and Maldisupporting

confidence: 51%

Intraspecific variations in Conus purpurascens injected venom using LC/MALDI-TOF-MS and LC-ESI-TripleTOF-MS

et al. 2015

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“…An alternative explanation for the observations on the behavioral cadre of Conus geographus that inject venom before completely engulfing their prey is that motor cabal components are used both for prey capture, as well as for defense. This is supported by findings of Dutertre et al (2014) on the presence of motor cabal toxins (μ-GIIIA and ω-GVIA) in the defense-evoked venom and a study by Bingham et al (2012) that showed that these compounds were also present in the predatory venom of C. geographus .. The ecological conditions of the Australian Conus geographus cadre presumably make direct injection of lightning-strike cabal components more effective than release into the water (but would therefore result in the snail only being able to capture one fish prey per foraging event).…”

supporting

confidence: 58%

“…See https://www.youtube.com/watch?v=FYh2zeAsRXY). However, a diversity of foraging behavior has been reported for Conus geographus from some Australian localities; as documented by Bingham and co-workers for Australian specimens (Bingham et al 2012). Even in this survey of Australian specimens, most C. geographus engulf their prey before envenomation, but a minority (5/27) were observed to extend their proboscis in the presence of prey.…”

mentioning

confidence: 84%

“…C. geographus that extend their proboscis towards fish prey are enriched in the Boult Reefs at the Great Barrier Reef in which staghorn coral is prevalent (Bingham et al 2012). This may be an environment in which releasing venom components and engulfing prey is a less effective strategy, selecting for behavior in which the snails directly inject lightning-strike cabal venom components into potential prey.…”

mentioning

confidence: 99%

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Linking neuroethology to the chemical biology of natural products: interactions between cone snails and their fish prey, a case study

et al. 2017

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From a biological perspective, a natural product can be defined as a compound evolved by an organism for chemical interactions with another organism including prey, predator, competitor, pathogen, symbiont or host. Natural products hold tremendous potential as drug leads and have been extensively studied by chemists and biochemists in the pharmaceutical industry. However, the biological purpose for which a natural product evolved is rarely addressed. By focusing on a well-studied group of natural products – venom components from predatory marine cone snails – this review provides a rationale for why a better understanding of the evolution, biology and biochemistry of natural products will facilitate both neuroscience and the potential for drug leads. The larger goal is to establish a new sub-discipline in the broader field of neuroethology that we refer to as “Chemical Neuroethology”, linking the substantial work carried out by chemists on natural products with accelerating advances in neuroethology.

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“…Despite Arg13 replacing the conserved Tyr13 critical for potent Ca v 2.2 inhibition in piscivorous ω-conotoxins 22 , 23 , the pharmacology of MoVIA and MoVIB closely resembles that of ω-conotoxins from fish-hunting cone snails, including those from C. consors , C. catus , C. fulmen , C. geographus , C. magus , C. radiatus , C. striatus and C. tulipa 22 , 23 , 38 , 43 , 44 . Indeed, MoVIA and/or MoVIB may be ancestral to GVIIA and/or GVIIB, given Tyr13 is also replaced by Arg13 and both have similar elongated and non-amidated C-termini, albeit those from C. geographus are ~100-fold lower affinity than the highly homologous GVIA at mammalian Ca v 2.2 16 , 45 . Similarly, the MVIIA-[Y13R] analogue also showed ~100-fold decrease in binding affinity over MVIIA and no functional activity at mammalian Ca v 2.2.…”

Section: Discussionmentioning

confidence: 99%

Novel analgesic ω-conotoxins from the vermivorous cone snail Conus moncuri provide new insights into the evolution of conopeptides

Sousa

McArthur

Brust

et al. 2018

Sci Rep

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Cone snails are a diverse group of predatory marine invertebrates that deploy remarkably complex venoms to rapidly paralyse worm, mollusc or fish prey. ω-Conotoxins are neurotoxic peptides from cone snail venoms that inhibit Cav2.2 voltage-gated calcium channel, demonstrating potential for pain management via intrathecal (IT) administration. Here, we isolated and characterized two novel ω-conotoxins, MoVIA and MoVIB from Conus moncuri, the first to be identified in vermivorous (worm-hunting) cone snails. MoVIA and MoVIB potently inhibited human Cav2.2 in fluorimetric assays and rat Cav2.2 in patch clamp studies, and both potently displaced radiolabeled ω-conotoxin GVIA (125I-GVIA) from human SH-SY5Y cells and fish brain membranes (IC50 2–9 pM). Intriguingly, an arginine at position 13 in MoVIA and MoVIB replaced the functionally critical tyrosine found in piscivorous ω-conotoxins. To investigate its role, we synthesized MoVIB-[R13Y] and MVIIA-[Y13R]. Interestingly, MVIIA-[Y13R] completely lost Cav2.2 activity and MoVIB-[R13Y] had reduced activity, indicating that Arg at position 13 was preferred in these vermivorous ω-conotoxins whereas tyrosine 13 is preferred in piscivorous ω-conotoxins. MoVIB reversed pain behavior in a rat neuropathic pain model, confirming that vermivorous cone snails are a new source of analgesic ω-conotoxins. Given vermivorous cone snails are ancestral to piscivorous species, our findings support the repurposing of defensive venom peptides in the evolution of piscivorous Conidae.

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Analysis of a cone snail's killer cocktail – The milked venom of Conus geographus

Cited by 20 publications

References 11 publications

Intraspecific variations in Conus purpurascens injected venom using LC/MALDI-TOF-MS and LC-ESI-TripleTOF-MS

Intraspecific variations in Conus purpurascens injected venom using LC/MALDI-TOF-MS and LC-ESI-TripleTOF-MS

Linking neuroethology to the chemical biology of natural products: interactions between cone snails and their fish prey, a case study

Novel analgesic ω-conotoxins from the vermivorous cone snail Conus moncuri provide new insights into the evolution of conopeptides

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