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Title: A conserved cysteine framework of toxins from Viola tricolor and Conus brunneus characterized in the Drosophila melanogaster Giant Fiber System.
Creator: Hoggard, Mickelene F., Mari, Frank, Graduate College
Abstract/Description: Conotoxins are disulfide rich peptides present in the venom of cone snails, a genus of marine mollusks that prey upon fish, worms, and other mollusks. Conotoxins are promising drugs leads with great prospects in the treatment of diseases and disorders such as chronic pain, multiple sclerosis and Parkinson’s and Alzheimer’s diseases. Similar compounds can be found in plants; for example, cyclotides, which are cyclic peptides isolated from the Violaceae violet, Rubiaceae coffee, and...
Show moreConotoxins are disulfide rich peptides present in the venom of cone snails, a genus of marine mollusks that prey upon fish, worms, and other mollusks. Conotoxins are promising drugs leads with great prospects in the treatment of diseases and disorders such as chronic pain, multiple sclerosis and Parkinson’s and Alzheimer’s diseases. Similar compounds can be found in plants; for example, cyclotides, which are cyclic peptides isolated from the Violaceae violet, Rubiaceae coffee, and Cucurbitaceae cucurbit families and they have a wide range of biological activities, such as anti-HIV, uterotonic, and antimicrobial. Cyclotides have a cyclic cysteine knot motif characterized by a cyclic backbone and six conserved cysteine residues that form the three disulfide bridges of the “knot”. This motif provides cyclotides with superior stability against thermal, chemical, and enzymatic degradation; marking them as potential frameworks for peptide drug delivery. Cysteine framework IX conotoxins C-C-C-CXC-C, isolated from the venom of Conus brunneus, contain the same cysteine framework, homologous sequences, and similar 3D structures to cyclotides. Presented are details on the isolation of these conotoxins and cyclotides, from Viola tricolor, and the characterization of their activity in the Drosophila melanogaster Giant Fiber System GFS, which contains GAP, acetylcholine, and glutamate synapses.
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Date Issued: 2014
PURL: http://purl.flvc.org/fau/fd/FA00005149
Format: Document (PDF)

Title: Conopeptides and methods of use.
Creator: Mari, Frank, Florida Atlantic University
Date Issued: 2006-01
PURL: http://purl.flvc.org/fcla/dt/15798
Format: Document (PDF)

Title: Use of Drosophila melanogaster larvae to evaluate cardioactive peptides.
Creator: Alishaev, Zahava, Godenschwege, Tanja A., Mari, Frank
Abstract/Description: Conopeptides are found in the venom of marine cone snails, aiding in the paralysis of their prey, and have been shown to have potential therapeutic uses in humans. Conopressins are conopeptides that target vasopressin/oxytocin receptors in vascular smooth muscle cells that are found within blood vessels. The crustacean cardioactive peptide (CCAP) is a homologous peptide found in crustaceans and has been shown to behave as a cardioaccelerator in a homologous system. This study describes the...
Show moreConopeptides are found in the venom of marine cone snails, aiding in the paralysis of their prey, and have been shown to have potential therapeutic uses in humans. Conopressins are conopeptides that target vasopressin/oxytocin receptors in vascular smooth muscle cells that are found within blood vessels. The crustacean cardioactive peptide (CCAP) is a homologous peptide found in crustaceans and has been shown to behave as a cardioaccelerator in a homologous system. This study describes the effects of CCAP in Drosophila larvae. We find that CCAP has an inotropic effect by causing a change in the contraction of blood vessels. We further investigate the effects of another possibly cardioactive conopeptide, γ-conopressin-vil, in Drosophila larvae. Elucidating the effects of conopetides in Drosophila larvae may translate to cardioactive therapeutic uses in mammalian systems.
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Date Issued: 2014
PURL: http://purl.flvc.org/fau/fd/FA0005000
Subject Headings: College students --Research --United States.
Format: Document (PDF)

Title: Conserved toxin framework between cone snail and violet plant.
Creator: Hoggard, Mickelene F., Mari, Frank, Graduate College
Date Issued: 2013-04-12
PURL: http://purl.flvc.org/fcla/dt/3361932
Subject Headings: Conotoxins, Snails, Conus, Cyclotides, Viola tricolor
Format: Document (PDF)

Title: New Tools for Targeted Disruption of Cholinergic Synaptic Transmission in Drosophila melanogaster.
Creator: Mejia, Monica, Heghinian, Mari D., Mari, Frank, Godenschwege, Tanja A., McCabe, Brian D.
Abstract/Description: Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels. The a7 subtype of nAChRs is involved in neurological pathologies such as Parkinson’s disease, Alzheimer’s disease, addiction, epilepsy and autism spectrum disorders. The Drosophila melanogaster a7 (Da7) has the closest sequence homology to the vertebrate a7 subunit and it can form homopentameric receptors just as the vertebrate counterpart. The Da7 subunits are essential for the function of the Giant Fiber...
Show moreNicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels. The a7 subtype of nAChRs is involved in neurological pathologies such as Parkinson’s disease, Alzheimer’s disease, addiction, epilepsy and autism spectrum disorders. The Drosophila melanogaster a7 (Da7) has the closest sequence homology to the vertebrate a7 subunit and it can form homopentameric receptors just as the vertebrate counterpart. The Da7 subunits are essential for the function of the Giant Fiber circuit, which mediates the escape response of the fly. To further characterize the receptor function, we generated different missense mutations in the Da7 nAChR’s ligand binding domain. We characterized the effects of targeted expression of two UAS-constructs carrying a single mutation, D197A and Y195T, as well as a UAS-construct carrying a triple D77T, L117Q, I196P mutation in a Da7 null mutant and in a wild type background. Expression of the triple mutation was able to restore the function of the circuit in Da7 null mutants and had no disruptive effects when expressed in wild type. In contrast, both single mutations severely disrupted the synaptic transmission of Da7-dependent but not glutamatergic or gap junction dependent synapses in wild type background, and did not or only partially rescued the synaptic defects of the null mutant. These observations are consistent with the formation of hybrid receptors, consisting of D197A or Y195T subunits and wild type Da7 subunits, in which the binding of acetylcholine or acetylcholine-induced conformational changes of the Da7 receptor are altered and causes inhibition of cholinergic responses. Thus targeted expression of D197A or Y195T can be used to selectively disrupt synaptic transmission of Da7-dependent synapses in neuronal circuits. Hence, these constructs can be used as tools to study learning and memory or addiction associated behaviors by allowing the manipulation of neuronal processing in the circuits without affecting other cellular signaling.
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Date Issued: 2013-05-30
PURL: http://purl.flvc.org/fau/fd/FAUIR000083
Format: Citation

Title: Conopeptides and methods of use.
Creator: Mari, Frank, Fields, Gregg B., Florida Atlantic University
Date Issued: 2004-09
PURL: http://purl.flvc.org/fcla/dt/15821
Format: Document (PDF)

Title: Characterization and distribution of parvalbumin from selected fish species.
Creator: Ross, Cliff Ian., Florida Atlantic University, Hartmann, James X., Mari, Frank
Abstract/Description: Parvalbumins are acidic calcium-binding proteins found in large quantities in the white muscle fibers of cold-blooded vertebrates. Fish display two to seven parvalbumin isotypes that are species specific and thus constitute a valuable tool in the study of phylogenetic relationships, and as a specific biomarker for fish identification. Parvalbumins were isolated from a selected sample of marine teleosts and elasmobranchs. Purified isotypes were characterized via HPLC (gel filtration, and ion...
Show moreParvalbumins are acidic calcium-binding proteins found in large quantities in the white muscle fibers of cold-blooded vertebrates. Fish display two to seven parvalbumin isotypes that are species specific and thus constitute a valuable tool in the study of phylogenetic relationships, and as a specific biomarker for fish identification. Parvalbumins were isolated from a selected sample of marine teleosts and elasmobranchs. Purified isotypes were characterized via HPLC (gel filtration, and ion exchange), and electrophoresis (IEF, and SDS-PAGE). An indirect immunoassay was developed for the parvalbumin isotypes using monoclonal antibodies directed against the highly conserved calcium-binding site. Parvalbumins from selected fish species are compared and contrasted by standard biochemical and immunological methods.
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Date Issued: 1998
PURL: http://purl.flvc.org/fcla/dt/15536
Subject Headings: Fishes, Calcium-binding proteins, Globular proteins
Format: Document (PDF)

Title: New conopeptides from Conus jaspedius.
Creator: Williams, Orette St. Aubyn, Florida Atlantic University, Mari, Frank
Abstract/Description: Cone snails (genus conus) are marine gastropods of tropical waters. They capture their prey by envenomation and for this; they have evolved a highly efficient and diverse venom cocktail of proteins and peptides. This has elicited extreme interest in venom composition and their molecular targets. In this study, the venom of Conus jaspedius, a small Atlantic cone snail was extracted, venom components isolated and analyzed, by a combination of Size exclusion and High performance liquid...
Show moreCone snails (genus conus) are marine gastropods of tropical waters. They capture their prey by envenomation and for this; they have evolved a highly efficient and diverse venom cocktail of proteins and peptides. This has elicited extreme interest in venom composition and their molecular targets. In this study, the venom of Conus jaspedius, a small Atlantic cone snail was extracted, venom components isolated and analyzed, by a combination of Size exclusion and High performance liquid chromatography, NMR, Mass spectrometry and Edman sequencing. Here, four novel conopeptide sequences are reported, namely; an alpha conotoxin, a member of the A and O superfamilies and a new family.
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Date Issued: 2004
PURL: http://purl.flvc.org/fcla/dt/13303
Subject Headings: Venom, Gastropoda--Venom, Poisonous animals, Peptides--Structure
Format: Document (PDF)

Title: Novel conopeptides from Conus tessulatus.
Creator: Borges, Paula., Florida Atlantic University, Mari, Frank
Abstract/Description: Cone snails are predatory marine mollusks that utilize their peptide rich venom to capture prey, deter competitors and defend themselves. Each of the 1000 known species expresses over 100 conotoxins with little overlap between species. Most of these conotoxins selectively target a specific neuronal ion-channel or receptor. Because of their unprecedented diversity and specificity, they hold enormous potential as neuropharmacological agents, and as neuroscience research tools. In this study,...
Show moreCone snails are predatory marine mollusks that utilize their peptide rich venom to capture prey, deter competitors and defend themselves. Each of the 1000 known species expresses over 100 conotoxins with little overlap between species. Most of these conotoxins selectively target a specific neuronal ion-channel or receptor. Because of their unprecedented diversity and specificity, they hold enormous potential as neuropharmacological agents, and as neuroscience research tools. In this study, the venom of a common shallow water cone snail that thrives in the Indo-Pacific to the Panamic region, Conus tessulatus , was analyzed; conopeptide components of the venom were isolated and investigated by high performance liquid chromatography, nuclear magnetic resonance, mass spectrometry, and automated Edman degradation sequencing. Five new peptide sequences are herein reported, among which there are three members of the M superfamily, one alpha conotoxin, and a conophan. The novel peptides comprise a partial peptide library of this particular cone.
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Date Issued: 2005
PURL: http://purl.flvc.org/fcla/dt/13231
Subject Headings: Conus, Venom, Gastropoda--Venom, Peptides--Structure
Format: Document (PDF)

Title: Theoretical studies of the mechanism of the Wittig olefination reaction.
Creator: Restrepo, Albeiro A., Florida Atlantic University, Mari, Frank
Abstract/Description: The results we have obtained indicate that the common procedure of utilizing of the mythical Wittig half-reaction to theoretically describe the mechanism of the Wittig olefination reaction does not give consistent results when electron correlation is taken into account in the model hamiltonian. We propose that the reaction of Me3P=CH2 with formaldehyde is the smallest system that can be used to properly model the Wittig olefination reaction. The best compromise between accuracy and...
Show moreThe results we have obtained indicate that the common procedure of utilizing of the mythical Wittig half-reaction to theoretically describe the mechanism of the Wittig olefination reaction does not give consistent results when electron correlation is taken into account in the model hamiltonian. We propose that the reaction of Me3P=CH2 with formaldehyde is the smallest system that can be used to properly model the Wittig olefination reaction. The best compromise between accuracy and computational expense is to compute the molecular geometries with the HF/6-31G* methodology and the energy at the MP2/6-31G*/HF-6-31G* level. We applied the methodology that we have developed to the study of reaction of a series of stabilized, semistabilized and unstabilized ylides with acetaldehyde.
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Date Issued: 1997
PURL: http://purl.flvc.org/fcla/dt/15468
Subject Headings: Wittig reaction, Organic compounds--Synthesis
Format: Document (PDF)

Title: Variability in the venom of Conus regius.
Creator: Uribe-Benninghoff, Alejandro., Florida Atlantic University, Hartmann, James X., Mari, Frank
Abstract/Description: The venom of two different geographical populations of Conus regius has been isolated and characterized. Comparisons between the chromatographic profiles of the venom of these two populations exhibited similarities and differences among the venom's constituents. MALDI-TOF and PCR analysis techniques ratified the differences present in the venom of both populations. It is postulated that these differences could reflect the rapid adaptive nature of cone snails in an actual stage of speciation....
Show moreThe venom of two different geographical populations of Conus regius has been isolated and characterized. Comparisons between the chromatographic profiles of the venom of these two populations exhibited similarities and differences among the venom's constituents. MALDI-TOF and PCR analysis techniques ratified the differences present in the venom of both populations. It is postulated that these differences could reflect the rapid adaptive nature of cone snails in an actual stage of speciation. Molecular weights of the venom's constituents were compared with those of patented conopeptides in the Swiss Protein Database. Results of this comparison indicated that a number of the peptides isolated for both of the populations of C. regius had the same molecular weight as other patented conopeptides. In combination with the PCR analysis of these conopeptides, it has been proposed that some of the venom constituents of the venom of C. regius could have pharmacological applications for vertebrate systems.
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Date Issued: 1999
PURL: http://purl.flvc.org/fcla/dt/15746
Subject Headings: Conus--Venom
Format: Document (PDF)

Title: Isolation and characterization of neuroactive peptides from the venom of cone snail species.
Creator: Cano, Herminsul, Florida Atlantic University, Mari, Frank
Abstract/Description: The mam objective of the work described in this thesis is isolation and characterization of novel neuroactive peptides from the venom of cone snail species. The first section is an introduction about cone snails. The first chapter is dedicated to the analysis of the milked venom obtained from three different specimens of C. ermineus which is the only fish-hunter cone snail from the east Atlantic region. MALDI-TOF mass spectrometry analysis of two specimens showed an identical profile with all...
Show moreThe mam objective of the work described in this thesis is isolation and characterization of novel neuroactive peptides from the venom of cone snail species. The first section is an introduction about cone snails. The first chapter is dedicated to the analysis of the milked venom obtained from three different specimens of C. ermineus which is the only fish-hunter cone snail from the east Atlantic region. MALDI-TOF mass spectrometry analysis of two specimens showed an identical profile with all components of the venom being novel conopeptides. The third specimen showed a mass spectrometry profile with molecular weights corresponding to already reported conotoxins plus one additional new conopeptide. Ten new conotoxins were isolated from C. ermineus; seven of them have sequences corresponding to A-superfamily of conotoxins, specifically a-conotoxins family. Six of these seven conotoxins are the first a4/4 conotoxins isolated from the milked venom from any fish-hunter cone snail specimens; the other one is a a4/7 conotoxin similar sequence to the already reported a-EI from C. ermineus. Two more conotoxins that belong to the 0-superfamily have the same amino acid sequence with the only difference being a hydroxyproline residue instead of a proline at position 21 of the sequence. In the second chapter, four specimens of C. purpurascens, the only fish-hunter of the Eastern Pacific region were analyzed. One of the specimens was sacrified and the crude venom was dissected-out of the venom duct. For the three remaining live specimens the venom was obtained by the "milking" procedure. Mass spectrometry profiles were compared between dissected and milked venom and between milked venom from different specimens. Analysis showed both similarities and differences in the profiles of the dissected and the three milked venoms. A comparison of the three milked venoms found some differences. This analysis showed that one specimen expressed two isomorphs of a putative a4/4-conotoxin; the only difference was the presence of proline instead of hydroxyproline at position seven in the amino acid sequence. These a4/4-conotoxins are the second report of this sub-class of conotoxin from the milked venom of cone snails and they have sequence homology to the a4/4 conotoxins isolated from C. ermineus. The analysis of the MALDI-TOF MS/MS spectra of the Leu-contryphan-P conopeptide from C. purpurascens revealed that conotoxins with a single disulfide bond in the sequence behave as a linear peptide in the mass spectrometry experiment exhibiting a good fragmentation pattern. Using this information by comparing the MS/MS spectra we were able to identify L-contryphan-P conopeptide lacking the first Gly residue in the sequence. In the third chapter, three conotoxins with sequence homology to the omega-superfamily were isolated from the crude dissected venom of the worm-hunter cone snail C. vexillum. The precursor of one of these conotoxins was already characterized by another research group. Analysis and comparison of this precursor with already known precursor allowed us to hypothesize that these conotoxins were ro-conotoxins. Two of the three conotoxins have the same amino acid sequence with hydroxyproline instead a proline in the structure. These conotoxins were the first ones isolated from the venom duct of these cone snail species. Several conotoxins had been reported from C. vexillum but they were isolated using eDNA cloning techniques. Chapter four shows the analysis of the worm-hunter cone snail C. pseudoarantius crude venom. Eight novel conotoxins were isolated from the pooled duct dissected venom from different specimens. The first was a a4/3-conotoxin with a carboxyglutamate residue present at position one in the sequence. Five more conotoxins with conotoxin frameworks and sequences similar to M-superfamily of conotoxins were also found; additionally, two more novel conotoxins with sequence homology to o-conotoxins from the S-superfamily were isolated. All the above conotoxins were analyzed by comparison of their structures against sequences of known conotoxins. All 23 conotoxins found in this research are novel conopeptides isolated from cone snail specimens. Future work on the activity these conotoxins will be important in the search for possible drugs in treatment of many diseases.
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Date Issued: 2005
PURL: http://purl.flvc.org/fcla/dt/12185
Subject Headings: Peptides--Structure, Gastropoda--Venom, Conus, Mass spectrometry--Analysis
Format: Document (PDF)

Title: Isolation and characterization of novel conopeptides from Conus dalli.
Creator: Abbasi, Husam Usama., Florida Atlantic University, Mari, Frank
Abstract/Description: Conus dalli is a cone snail species that preys upon mollusks (molluscivorous) and it belongs to the same clade as the better studied Conus textile. They have different biogeographical distribution: C. dalli is restricted to the Panamic area; whereas C. textile is a widespread species found from the Red Sea to Hawaii. The venom of C. textile is an extremely complex mixture of conopeptides characterized for their very high content of modified amino acids; particularly, for their high content of...
Show moreConus dalli is a cone snail species that preys upon mollusks (molluscivorous) and it belongs to the same clade as the better studied Conus textile. They have different biogeographical distribution: C. dalli is restricted to the Panamic area; whereas C. textile is a widespread species found from the Red Sea to Hawaii. The venom of C. textile is an extremely complex mixture of conopeptides characterized for their very high content of modified amino acids; particularly, for their high content of gamma-carboxy glutamate (Gla). Therefore, it is expected that the venom of C. dalli is equally complex and it might provide us with a library of novel conopeptides. We have collected 6 specimens of C. dalli from the Pacific coast of Panama. Their venom ducts were dissected and 40 mg of crude venom were extracted. Venom was separated using SE-HPLC and RP-HPLC and several single-component fractions with unique molecular weights have been found. 1D and 2D NMR methods in conjunction with mass spectrometry techniques have been applied to the main components of the venom. Three novel conopeptides have been isolated and characterized; dal_C1011h, dal_C0910, and dal_C0805g. dal_C1011h is a 27-residue hydrophobic conotoxin that belongs to O-superfamily, dal_C0910 is a 16-residue conotoxin that belongs to M-superfamily, and dal_C0805g is a 12-residue linear conopeptide the belong to the Conorfamide family. The details on the characterization of these conopeptides along with a comparison with previous data obtained from C. textile are presented.
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Date Issued: 2005
PURL: http://purl.flvc.org/fcla/dt/13214
Subject Headings: Conus, Gastropoda--Venom, Venom
Format: Document (PDF)

Title: Isolation and characterization of novel conopeptides from Conus nux.
Creator: Ramlakhan, Rani Elizabeth., Florida Atlantic University, Mari, Frank
Abstract/Description: Cone snails are marine gastropods belonging to the genus Conus that inhabit in tropical habitats throughout the world. They are predators that paralyze their prey by injection of venom, containing a complex mixture of conopeptides. The venom of cone snails has been found to be a valuable source of specific drugs for disorders ranging from stroke to chronic pain. For this work, the venom of Conus nux, a Panamic cone snail species, was extracted and analyzed. Components of the venom were...
Show moreCone snails are marine gastropods belonging to the genus Conus that inhabit in tropical habitats throughout the world. They are predators that paralyze their prey by injection of venom, containing a complex mixture of conopeptides. The venom of cone snails has been found to be a valuable source of specific drugs for disorders ranging from stroke to chronic pain. For this work, the venom of Conus nux, a Panamic cone snail species, was extracted and analyzed. Components of the venom were isolated using Size Exclusion Chromatography (SEC) and Reversed Phase High Performance Liquid Chromatography techniques. A novel conopeptide sequence, determined by Edman Degradation is reported. The arrangement of the cysteines residues within this sequence suggest that it member of the M-superfamily of conotoxins.
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Date Issued: 2002
PURL: http://purl.flvc.org/fcla/dt/12951
Subject Headings: Conus, Gastropoda--Venom, Venom
Format: Document (PDF)

Title: Isolation and characterization of novel conopeptides from Conus brunneus.
Creator: Pellicier, Jalidsa., Florida Atlantic University, Mari, Frank
Abstract/Description: Cone snails are predatory marine mollusks found in the genus Conus that use a complex cocktail of peptides to capture prey and deter predators. Most of the venom components selectively target ion channels or receptors, making them invaluable tools in neurophysiological studies. In this study, the venom of Conus brunneus, a common Panamic vermivorous cone snail species, was characterized by the use of high performance liquid chromatography, nuclear magnetic resonance, mass spectrometry, and...
Show moreCone snails are predatory marine mollusks found in the genus Conus that use a complex cocktail of peptides to capture prey and deter predators. Most of the venom components selectively target ion channels or receptors, making them invaluable tools in neurophysiological studies. In this study, the venom of Conus brunneus, a common Panamic vermivorous cone snail species, was characterized by the use of high performance liquid chromatography, nuclear magnetic resonance, mass spectrometry, and automated Edman degradation sequencing. Three novel peptide sequences were reported: two peptides were members of the M-superfamily and one peptide was classified as an alpha-conotoxin. The disulfide connectivity of a previously isolated P-conotoxin was also determined. These peptides comprise a partial peptide library of Conus brunneus and may prove useful in numerous structural and neurological studies.
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Date Issued: 2006
PURL: http://purl.flvc.org/fcla/dt/13365
Subject Headings: Conus, Gastropoda--Venom, Venom, Peptides--Structure
Format: Document (PDF)

Title: Three-dimensional structure of the alpha-conotoxin EI determined by proton NMR spectroscopy.
Creator: Franco, Aldo, Florida Atlantic University, Mari, Frank
Abstract/Description: The alpha-conotoxin EI is an 18-residue peptide (RDOCCYHPTCNMSNPQIC; 4-10, 5-18) isolated from the venom of Conus ermineus. This peptide targets the nicotinic acetylcholine receptor (nAChR) found in mammalian skeletal muscle and the electric organ of Torpedo. 2D-NMR methods and dynamical simulated annealing protocols have been used to determine the 3D structure of EI. 133 NOE-derived distances were used to produce 13 structures with minimum energy that complied with the NOE restraints. The...
Show moreThe alpha-conotoxin EI is an 18-residue peptide (RDOCCYHPTCNMSNPQIC; 4-10, 5-18) isolated from the venom of Conus ermineus. This peptide targets the nicotinic acetylcholine receptor (nAChR) found in mammalian skeletal muscle and the electric organ of Torpedo. 2D-NMR methods and dynamical simulated annealing protocols have been used to determine the 3D structure of EI. 133 NOE-derived distances were used to produce 13 structures with minimum energy that complied with the NOE restraints. The structure of EI is characterized by a helical loop between T9 and M12 that is stabilized by the C4-C10 disulfide bond and turns involving C4-C5 and N14-P15. The overall fold of EI is similar to that of other alpha4/7 conotoxins (PnIA/B, MII, EpI). However, unlike these other alpha4/7 conotoxins, EI targets the muscular type nAChR. The differences in selectivity can be attributed to the surface charge distribution among these alpha4/7 conotoxins.
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Date Issued: 1998
PURL: http://purl.flvc.org/fcla/dt/15609
Subject Headings: Conus--Venom, Peptides--Structure, Nuclear magnetic resonance spectroscopy
Format: Document (PDF)

Title: Discovery and biological characterization of conotoxins from the venom of Conus Brunneus in Drosophila Melanogaster.
Creator: Heghinian, Mari D., Mari, Frank, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: Cone snails are venomous marine predators whose venom is a complex mixture of modified peptides (conopeptides). Conopeptides have direct specificity towards voltage- and ligand-gated ion channels and G-protein coupled receptors. More specifically, alpha conotoxins target nicotinic acetylcholine receptors (nAChR) and are of great interest as probes for different nAChR subtypes involved in a broad range of neurological function. Typically, the amount of peptide provided directly from the cone...
Show moreCone snails are venomous marine predators whose venom is a complex mixture of modified peptides (conopeptides). Conopeptides have direct specificity towards voltage- and ligand-gated ion channels and G-protein coupled receptors. More specifically, alpha conotoxins target nicotinic acetylcholine receptors (nAChR) and are of great interest as probes for different nAChR subtypes involved in a broad range of neurological function. Typically, the amount of peptide provided directly from the cone snails (from either dissected or “milked” venom) is minimal, thus hindering the wide use of bioassay-guided approaches for compound discovery. Biochemical-based approaches for discovery by means of identification and characterization of venom components can be used due to their compatibility with the small quantities of cone snail venom available; however, no direct assessment of the bioactivity can be gleaned from these approaches. Therefore, newly discovered conotoxins must be acquired synthetically, which can be difficult due to their complicated folding motifs. The ability to test small quantities of peptide for bioactivity during the purification process can lead to the discovery of novel components using more direct approaches. Presented here is the description of use of an effective method of bioassay-guided fractionation for the discovery of novel alpha conotoxins as well as further biological characterization of other known alpha conotoxins. This method requires minimal amounts of sample and evaluates, via in vivo electrophysiological measurements, the effect of conotoxins on the functional outputs of a well-characterized neuronal circuit in Drosophila melanogaster known as the giant fiber system. Our approach uses reversed-phase HPLC fractions from venom dissected from the ducts of Conus brunneus in addition to synthetic alpha conotoxins. Fractions were individually tested for activity, re-fractionated, and re-tested to narrow down the compound responsible for activity. A novel alpha conotoxin, bru1b, was discovered via the aforementioned approach. It has been fully characterized in the giant fiber system through the use of mutant flies, as well as tested in Xenopus oocytes expressing nicotinic acetylcholine channels and against the acetylcholine binding protein. Other well-known alpha conotoxins have also been characterized in the giant fiber system.
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Date Issued: 2014
PURL: http://purl.flvc.org/fau/fd/FA00004122, http://purl.flvc.org/fau/fd/FA00004122
Subject Headings: Drosophila melanogaster, Gastropoda -- venom, Peptides -- Structure, Venom
Format: Document (PDF)

Title: Broad Application of Conotoxins As Molecular Probes, Therapeutic Leads and Drug Delivery Vectors In Excitable and Non-Excitable Systems.
Creator: Padilla, Alberto, Hartmann, James X., Mari, Frank, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Conotoxins are peptides expressed by the exogenome of more than 800 species of marine mollusks belonging to the genus Conus (cone snails.) Owing to their high specificity and affinity for ion channels, transporter molecules, and cell receptors of the central and peripheral nervous systems, conotoxins have been investigated for nearly four decades. These efforts on conotoxin research made possible the FDA approved use of Ziconitide/Prialt, a conotoxin derived from the venom of Conus magus,...
Show moreConotoxins are peptides expressed by the exogenome of more than 800 species of marine mollusks belonging to the genus Conus (cone snails.) Owing to their high specificity and affinity for ion channels, transporter molecules, and cell receptors of the central and peripheral nervous systems, conotoxins have been investigated for nearly four decades. These efforts on conotoxin research made possible the FDA approved use of Ziconitide/Prialt, a conotoxin derived from the venom of Conus magus, which effectively treats patients suffering from severe chronic pain without consequent narcotic effects. Additionally, six other conotoxins have reached clinical trials and many novel ones are being discovered every day. Investigations reported in this dissertation broadens the applicability of conotoxins to non-excitable systems. Here, conotoxins from the dissected venom of the vermivorous cone snail Conus nux were isolated and purified by size exclusion and reverse phase HPLC and characterized by MALDI-TOF and MS/MS spectrometry. The purified conopeptide fractions revealed: 1) antagonist activity of conotoxin NuxVID on two human voltage-gated sodium channels, displaying capabilities as a practical molecular probe and a potential therapeutic lead. 2) Ability for two novel conotoxins to traverse artificial biological membranes, suggesting their potential as drug delivery systems. 3) In vitro capacity of several novel conopeptides to interfere with the adhesion of PfEMP1 domains, expressed in P. falciparum infected erythrocytes, to vascular endothelial and placenta receptors. Lastly, this work reveals binding of the synthetic form of α-conotoxin ImI, from the vermivorous cone snail Conus imperialis, to the α7 nAChR of macrophage-like-cells derived from the pre-monocytic leukemic cell line THP-1 in support of the involvement of this receptor in the cholinergic anti-inflammatory pathway.
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Date Issued: 2019
PURL: http://purl.flvc.org/fau/fd/FA00013250
Subject Headings: Conotoxins, Drug Delivery Systems, Molecular Probes
Format: Document (PDF)

Title: Isocation and characterization of conotoxins from the venom of Conus Planorbis and Conus Ferrugineus.
Creator: Pak, Adriana, Mari, Frank, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: The venom of marine gastropods belonging to the genus Conus has yielded numerous structurally and functionally diverse peptidic components. The increase variety of bioactive peptides identified in cone snail venoms is the product of the variety of molecular adaptations taken by Conus species in evolving neuroactive molecules to suit their diverse biological purposes. Toxins from cone snails are classified into two major groups. One group consists of disulfide-rich peptides commonly termed...
Show moreThe venom of marine gastropods belonging to the genus Conus has yielded numerous structurally and functionally diverse peptidic components. The increase variety of bioactive peptides identified in cone snail venoms is the product of the variety of molecular adaptations taken by Conus species in evolving neuroactive molecules to suit their diverse biological purposes. Toxins from cone snails are classified into two major groups. One group consists of disulfide-rich peptides commonly termed conotoxins; the second group comprises peptides with only one disulfide bond or none. In this work, we present the discovery and characterization from the marine snails C. planorbis and C. ferrugineus. Both species are commonly found in the Indo-Pacific region and are very similar and is not distinguishable by size and shape of the shell. Novel P and T-Supefamiles were found in both species along with small linear peptides with have a high frequency of tyrosine residues. Each chapter contains a detailed look at the discovery process for the isolation and characterization of C. planorbis and C. ferrugineus. At discussion part, we also compared the peptides isolated in this work with other peptides from the literature.
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Date Issued: 2014
PURL: http://purl.flvc.org/fau/fd/FA00004146, http://purl.flvc.org/fau/fd/FA00004146
Subject Headings: Conus, Gastropoda -- Venom, Peptides -- Structure, Venum
Format: Document (PDF)

Title: Peptidomic analysis and characterization of the venom from Conus purpurascens.
Creator: Rodriguez, Alena, Mari, Frank, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: The venom of cone snails is a potent cocktail of peptides, proteins, and other small molecules. Several of the peptides (conopeptides and conotoxins) target ion channels and receptors and have proven useful as biochemical probes or pharmaceutical leads. In this study, the venom of a fish-hunting cone snail, Conus purpurascens was analyzed for intraspecific variability; α-conotoxins from the venom were isolated by high performance liquid chromatography, identified by mass spectrometry and...
Show moreThe venom of cone snails is a potent cocktail of peptides, proteins, and other small molecules. Several of the peptides (conopeptides and conotoxins) target ion channels and receptors and have proven useful as biochemical probes or pharmaceutical leads. In this study, the venom of a fish-hunting cone snail, Conus purpurascens was analyzed for intraspecific variability; α-conotoxins from the venom were isolated by high performance liquid chromatography, identified by mass spectrometry and nuclear magnetic resonance, and tested in a electrophysiological assay in Drosophila melanogaster; the effects of diet change on venom composition was investigated. It has been determined that each specimen of C. purpurascens expresses a distinct venom, resulting in the expression of more than 5,000 unique conopeptides across the species. α- conotoxin PIA was shown to inhibit the Dα7 nicotinic acetylcholine receptor.
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Date Issued: 2015
PURL: http://purl.flvc.org/fau/fd/FA00004403, http://purl.flvc.org/fau/fd/FA00004403
Subject Headings: Conidae -- Environmental aspects, Drosophila melanogaster, Gastropoda -- Venom, Peptides -- Structure, Venom
Format: Document (PDF)

FAU Theses and Dissertations (14)	+ -
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Gastropoda--Venom (6)	+ -
Peptides--Structure (5)	+ -
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Conotoxins (2)	+ -
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abstract (1)	+ -

Mari, Frank (21)	+ -
Florida Atlantic University (16)	+ -
Charles E. Schmidt College of Science (4)	+ -
Department of Chemistry and Biochemistry (3)	+ -
Hartmann, James X. (3)	+ -

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