Cone snails are venomous marine gastropods that produce venom rich in neuroactive peptides, called conopeptides. The majority of published work on conopeptides has been from fish-hunting and mollusk-hunting cone snails. The work in this dissertation focuses on the discovery and characterization of novel conopeptides from the venom of worm-hunting cone snails. Eleven novel conopeptides have been isolated and biochemically characterized from the venom of C. nux using high performance liquid chromatography for the isolation and purification, and mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy were used for the biochemical characterization of the conopeptides. Nano-NMR spectroscopy was used as a tool to elucidate the three-dimensional structures of four conotoxins using native quantities of peptide isolated from the venom of C. nux, C. villepinii, and C. regius. In addition, the sequence-specific assignments and molecular model of a conotoxin from the venom of C. flo ridanus was also completed. The first chapter reviews the known conotoxin three-dimensional structures and cystine-constrained frameworks. The second chapter presents the mini-M conotoxins isolated from the venom of C. nux. The third chapter presents the three-dimensional NMR solution structure of a mini-M conotoxin from the venom of C. regius. The fourth chapter presents the cysteine-free conopeptides isolated from the venom of C. nux; conorfamide-nux1, a RFamide-related peptide, and nux770, a short pentapeptide. The fifth chapter presents the T-superfamily conotoxins isolated from the venom of C. nux, as well as the three-dimensional solution structure of one of the T-superfamily conotoxins. The sixth chapter presents the NMR solution structure of the first conotoxin with a cysteine-stabilized helix-loop-helix fold. / Finally, the seventh chapter presents the O-superfamily conotoxins isolated from the venom of C. nux, as well as the three-dimensional solution structure of one of the O- superfamily conotoxins with an unusually knotted fold. This work shows the vast structural diversity of peptides that cone snails continue to engineer. / by Sanaz Dovell. / Thesis (Ph.D.)--Florida Atlantic University, 2010. / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2010. Mode of access: World Wide Web.

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 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. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2014. / FAU Electronic Theses and Dissertations Collection

by Fred. C. Pflueger. / Thesis (Ph.D.)--Florida Atlantic University, 2008. / Includes bibliographical references at end of each chapter. / Cone snails are predatory marine gastropods that use venom for means of predation and defense. This venom is a complex mixture of conopeptides that selectivity binds to ion channels and receptors, giving them a wide range of potential pharmaceutical applications. Conus brunneus is a wide spread Eastern Pacific cone snail species that preys upon worms (vermivorous). Vermivorous cone snails have developed very specific biochemical strategies for the immobilization of their prey and their venom has not been extensively studied to date. The main objective of this dissertation is the characterization of novel conopeptides isolated from Conus brunneus. Chapter 1 is an introduction and background on cone snails and conopeptides. Chapter 2 details the isolation and characterization of a novel P-superfamily conotoxin. Chapter 3 presents the 3D solution structure of the novel P-superfamily conotoxin. Chapter 4 details the isolation and characterization of two novel M-superfamily conotoxins. Chapter 5 covers the use of nano-NMR to characterize a novel P-superfamily conotoxin using nanomole quantities of sample. Chapter 6 is a reprint of a paper published in the Journal of the American Chemical Society in which we combined and implemented techniques developed in the previous chapters to report the presence of D-(Sd(B-Hydroxyvaline in a polypeptide chain. This dissertation contains the first reported work of a P-superfamily structure obtained directly from the crude venom therefore accurately representing native post-translational modifications. In this paper, crude cone snail venom was characterized by: high performance liquid chromatography, nuclear magnetic resonance spectroscopy, nanonuclear magnetic resonance spectroscopy, mass spectrometry, amino acid analysis, Edman degradation sequencing, and preliminary bioassays.

Typescript. / Thesis--University of Hawaii, 1964. / Bibliography: leaves 124-126. / xiii, 126 leaves ill. (part mounted, part col.), tables

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A mini dissertation submitted in partial compliance with the requirements for M.Tech.: Homoeopathy, Durban Institute of Technology, 2004. / The purpose of this investigation was to determine the effects of the thirtieth centesimal (30CH) potency of the venom of Bitis gabonica gabonica on healthy individuals in order to elucidate the total morbid symptomatology produced by the drug so that it may be prescribed by Homoeopathic practitioners according to the Law of Similars, as is required by Homoeopathic methodology. It was hypothesized that the 30CH potency of Bitis gabonica gabonica would produce clearly observable signs and symptoms in healthy Provers. / M

Class of 2010 Abstract / OBJECTIVES: To determine the clinical significance of a population of scorpions, C. sculpturatus, found in New Mexico. This includes the toxicity of the venom as well as the interactions of venom and antivenom. METHODS: This project will include a descriptive retrospective study of clinical and laboratory data obtained through a patient chart and analytical laboratory procedures to positively identify the species of scorpion responsible for the envenomation. Scorpion Collection Scorpions from the location of the reported sting will be collected for venom analysis. Specific details and directions will be obtained from the grandparent of the victim regarding the campsite at Caballo Lake State Park. Human Subject – N/A Sample Size The sample size of specimens needed should be a minimum of 50 scorpions. This is due to factors which include; extremely small volumes of venom produced by each individual, the possibility of no venom production, damaged telson during collection (anatomical feature used in the delivery of venom), size variation in specimens and short window of opportunity to collect. Since these scorpions are more active during summer months, and travel time must also be accounted for, only a few months a year are acceptable. Instrumentation and Variables This is primarily laboratory assays rather than clinical. The clinical aspect, a case study involving the victim of a scorpion envenomation, was the reason behind needing to identify this Centruroides species. The analytical laboratory findings will be what will determine the exact species of Centruroides. A number of laboratory instrumentations and tests will be used or performed. These include; sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), SDS-PAGE with hyaluronic acid, turbidimetric absorbances of hyaluronidase, reverse phase high pressure liquid chromatography (RPHPLC), enzyme-linked immunosorbent assay (ELISA), lethal dose 50 (LD%) and effective dose 50 (ED50). Variables regarding these findings will include two main factors; the human factor and the instrumentation factor. First the human factor, samples collected must remain free of contaminants up to the point of analysis. The instruments RESULTS: 104 specimens were collected at Caballo Lake State Park. Four of these specimens were sent to a taxonomist and identified as C. sculpturatus. SDS-PAGE, turbidimetric HA, and RPHPLC showed no significant difference in venom between the New Mexico and Arizona Centruroides, but did show a significant difference between these two groups and the Mexico Centruroides. SDS-PAGE/HA and ELISA assays showed no significant differences between groups. LD50 and ED50 data were similar between New Mexico and Mexico Centruroides, both being more potent and more readily reversed by antivenom than the Arizona Centruroides. CONCLUSIONS: The assays which show possible differences between species, SDS-PAGE, SDS-PAGE-HA, turbidimetric HAase, RPHPLC, and ELISA were all identical between the New Mexico Centruroides species and the Arizona Centruroides sculpturatus. These findings were opposite when comparing New Mexico Centruroides species and the Mexico Centruroides limpidus limpidus. Three of the five assays showed a significant difference. Since the Mexico Centruroides limpidus limpidus is a known different species, this was expected. With this data the scorpion specimens collected in New Mexico have been identified as Centruroides sculpturatus. An interesting difference between the New Mexico and Arizona Centruroides sculpturatus was toxicity of the venom. The New Mexico groups had close to a two fold increase in toxicity. In fact, the toxicity of the New Mexico groups was equivalent to the Mexico Centruroides limpidus limpidus which is well documented as having an increased toxicity.

Wing-ming Keung. / Thesis (M.Ph.)--Chinese University of Hong Kong. / Bibliography: l. 81-87.

Thesis (Ph.D.) -- University of Adelaide, Dept. of Paediatrics, 2000. / Includes bibliographical references.