Peptide neurotoxins from the marine fish-hunting snails of the genus CONUS. They contain 13 to 29 amino acids which are strongly basic and are highly cross-linked by disulfide bonds. There are three types of conotoxins, omega-, alpha-, and mu-. OMEGA-CONOTOXINS inhibit voltage-activated entry of calcium into the presynaptic membrane and therefore the release of ACETYLCHOLINE. Alpha-conotoxins inhibit the postsynaptic acetylcholine receptor. Mu-conotoxins prevent the generation of muscle action potentials. (From Concise Encyclopedia Biochemistry and Molecular Biology, 3rd ed)
A genus of cone-shaped marine snails in the family Conidae, class GASTROPODA. It comprises more than 600 species, many containing unique venoms (CONUS VENOMS) with which they immobilize their prey.
Venoms from mollusks, including CONUS and OCTOPUS species. The venoms contain proteins, enzymes, choline derivatives, slow-reacting substances, and several characterized polypeptide toxins that affect the nervous system. Mollusk venoms include cephalotoxin, venerupin, maculotoxin, surugatoxin, conotoxins, and murexine.
Marine, freshwater, or terrestrial mollusks of the class Gastropoda. Most have an enclosing spiral shell, and several genera harbor parasites pathogenic to man.
Drugs that bind to nicotinic cholinergic receptors (RECEPTORS, NICOTINIC) and block the actions of acetylcholine or cholinergic agonists. Nicotinic antagonists block synaptic transmission at autonomic ganglia, the skeletal neuromuscular junction, and at central nervous system nicotinic synapses.
Chemical groups containing the covalent disulfide bonds -S-S-. The sulfur atoms can be bound to inorganic or organic moieties.
Toxic substances from microorganisms, plants or animals that interfere with the functions of the nervous system. Most venoms contain neurotoxic substances. Myotoxins are included in this concept.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
A class of drugs that act by inhibition of sodium influx through cell membranes. Blockade of sodium channels slows the rate and amplitude of initial rapid depolarization, reduces cell excitability, and reduces conduction velocity.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
One of the two major classes of cholinergic receptors. Nicotinic receptors were originally distinguished by their preference for NICOTINE over MUSCARINE. They are generally divided into muscle-type and neuronal-type (previously ganglionic) based on pharmacology, and subunit composition of the receptors.
Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.
Processes involved in the formation of TERTIARY PROTEIN STRUCTURE.
An aquatic genus of the family, Pipidae, occurring in Africa and distinguished by having black horny claws on three inner hind toes.
The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.
The basic subunit of beta-crystallins.
Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve.
Subjective cutaneous sensations (e.g., cold, warmth, tingling, pressure, etc.) that are experienced spontaneously in the absence of stimulation.
Works containing information articles on subjects in every field of knowledge, usually arranged in alphabetical order, or a similar work limited to a special field or subject. (From The ALA Glossary of Library and Information Science, 1983)
An unpleasant sensation induced by noxious stimuli which are detected by NERVE ENDINGS of NOCICEPTIVE NEURONS.
Penetrating and non-penetrating injuries to the spinal cord resulting from traumatic external forces (e.g., WOUNDS, GUNSHOT; WHIPLASH INJURIES; etc.).
Scales, questionnaires, tests, and other methods used to assess pain severity and duration in patients or experimental animals to aid in diagnosis, therapy, and physiological studies.
Peripheral, autonomic, and cranial nerve disorders that are associated with DIABETES MELLITUS. These conditions usually result from diabetic microvascular injury involving small blood vessels that supply nerves (VASA NERVORUM). Relatively common conditions which may be associated with diabetic neuropathy include third nerve palsy (see OCULOMOTOR NERVE DISEASES); MONONEUROPATHY; mononeuropathy multiplex; diabetic amyotrophy; a painful POLYNEUROPATHY; autonomic neuropathy; and thoracoabdominal neuropathy. (From Adams et al., Principles of Neurology, 6th ed, p1325)
An antifibrinolytic agent that acts by inhibiting plasminogen activators which have fibrinolytic properties.
Compounds capable of relieving pain without the loss of CONSCIOUSNESS.
Amino derivatives of caproic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the amino caproic acid structure.
Electric conductors through which electric currents enter or leave a medium, whether it be an electrolytic solution, solid, molten mass, gas, or vacuum.
The study of chemical changes resulting from electrical action and electrical activity resulting from chemical changes.
A reagent used for the determination of iron.
Energy transmitted from the sun in the form of electromagnetic radiation.
The utilization of an electrical current to measure, analyze, or alter chemicals or chemical reactions in solution, cells, or tissues.
Techniques used for determining the values of photometric parameters of light resulting from LUMINESCENCE.
A hard, brittle, grayish-white rare earth metal with an atomic symbol Ru, atomic number 44, and atomic weight 101.07. It is used as a catalyst and hardener for PLATINUM and PALLADIUM.
Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level.
Management of public health organizations or agencies.
State plans prepared by the State Health Planning and Development Agencies which are made up from plans submitted by the Health Systems Agencies and subject to review and revision by the Statewide Health Coordinating Council.
The activities and endeavors of the public health services in a community on any level.
Programs of surveillance designed to prevent the transmission of disease by any means from person to person or from animal to man.

Ultra-slow inactivation in mu1 Na+ channels is produced by a structural rearrangement of the outer vestibule. (1/410)

While studying the adult rat skeletal muscle Na+ channel outer vestibule, we found that certain mutations of the lysine residue in the domain III P region at amino acid position 1237 of the alpha subunit, which is essential for the Na+ selectivity of the channel, produced substantial changes in the inactivation process. When skeletal muscle alpha subunits (micro1) with K1237 mutated to either serine (K1237S) or glutamic acid (K1237E) were expressed in Xenopus oocytes and depolarized for several minutes, the channels entered a state of inactivation from which recovery was very slow, i.e., the time constants of entry into and exit from this state were in the order of approximately 100 s. We refer to this process as "ultra-slow inactivation". By contrast, wild-type channels and channels with the charge-preserving mutation K1237R largely recovered within approximately 60 s, with only 20-30% of the current showing ultra-slow recovery. Coexpression of the rat brain beta1 subunit along with the K1237E alpha subunit tended to accelerate the faster components of recovery from inactivation, as has been reported previously of native channels, but had no effect on the mutation-induced ultra-slow inactivation. This implied that ultra-slow inactivation was a distinct process different from normal inactivation. Binding to the pore of a partially blocking peptide reduced the number of channels entering the ultra-slow inactivation state, possibly by interference with a structural rearrangement of the outer vestibule. Thus, ultra-slow inactivation, favored by charge-altering mutations at site 1237 in micro1 Na+ channels, may be analogous to C-type inactivation in Shaker K+ channels.  (+info)

NMR spatial structure of alpha-conotoxin ImI reveals a common scaffold in snail and snake toxins recognizing neuronal nicotinic acetylcholine receptors. (2/410)

A 600 MHz NMR study of alpha-conotoxin ImI from Conus imperialis, targeting the alpha7 neuronal nicotinic acetylcholine receptor (nAChR), is presented. ImI backbone spatial structure is well defined basing on the NOEs, spin-spin coupling constants, and amide protons hydrogen-deuterium exchange data: rmsd of the backbone atom coordinates at the 2-12 region is 0.28 A in the 20 best structures. The structure is described as a type I beta-turn (positions 2-5) followed by a distorted helix (positions 5-11). Similar structural patterns can be found in all neuronal-specific alpha-conotoxins. Highly mobile side chains of the Asp-5, Arg-7 and Trp-10 residues form a single site for ImI binding to the alpha7 receptor. When depicted with opposite directions of the polypeptide chains, the ImI helix and the tip of the central loop of long chain snake neurotoxins demonstrate a common scaffold and similar positioning of the functional side chains, both of these structural elements appearing essential for binding to the neuronal nAChRs.  (+info)

A conotoxin from Conus textile with unusual posttranslational modifications reduces presynaptic Ca2+ influx. (3/410)

Cone snails are gastropod mollusks of the genus Conus that live in tropical marine habitats. They are predators that paralyze their prey by injection of venom containing a plethora of small, conformationally constrained peptides (conotoxins). We report the identification, characterization, and structure of a gamma-carboxyglutamic acid-containing peptide, conotoxin epsilon-TxIX, isolated from the venom of the molluscivorous cone snail, Conus textile. The disulfide bonding pattern of the four cysteine residues, an unparalleled degree of posttranslational processing including bromination, hydroxylation, and glycosylation define a family of conotoxins that may target presynaptic Ca2+ channels or act on G protein-coupled presynaptic receptors via another mechanism. This conotoxin selectively reduces neurotransmitter release at an Aplysia cholinergic synapse by reducing the presynaptic influx of Ca2+ in a slow and reversible fashion. The three-dimensional structure, determined by two-dimensional 1H NMR spectroscopy, identifies an electronegative patch created by the side chains of two gamma-carboxyglutamic acid residues that extend outward from a cavernous cleft. The glycosylated threonine and hydroxylated proline enclose a localized hydrophobic region centered on the brominated tryptophan residue within the constrained intercysteine region.  (+info)

Solution structure of alpha-conotoxin ImI determined by two-dimensional NMR spectroscopy. (4/410)

The three-dimensional structure of alpha-conotoxin ImI, a potent antagonist targeting the neuronal alpha7 subtype of nicotinic acetylcholine receptor (nAChR), has been investigated by NMR spectroscopy. On the basis of 181 experimental constraints, a total of 25 converged structures were obtained. The average pairwise atomic root mean square difference is 0.40+/-0.11 A for the backbone atoms. The resulting structure indicates the presence of two successive type I beta-turns and a 310 helix for residues Cys2-Cys8 and Ala9-Arg11, respectively, and shows a significant structural similarity to that of alpha-conotoxin PnIA, which is also selective for the neuronal nAChR.  (+info)

Pairwise interactions between neuronal alpha7 acetylcholine receptors and alpha-conotoxin ImI. (5/410)

The present work uses alpha-conotoxin ImI (CTx ImI) to probe the neurotransmitter binding site of neuronal alpha7 acetylcholine receptors. We identify key residues in alpha7 that contribute to CTx ImI affinity, and use mutant cycles analysis to identify pairs of residues that stabilize the receptor-conotoxin complex. We first mutated key residues in the seven known loops of alpha7 that converge at the subunit interface to form the ligand binding site. The mutant subunits were expressed in 293 HEK cells, and CTx ImI binding was measured by competition against the initial rate of 125I-alpha-bungarotoxin binding. The results reveal a predominant contribution by Tyr-195 in alpha7, accompanied by smaller contributions by Thr-77, Tyr-93, Asn-111, Gln-117, and Trp-149. Based upon our previous identification of bioactive residues in CTx ImI, we measured binding of receptor and toxin mutations and analyzed the results using thermodynamic mutant cycles. The results reveal a single dominant interaction between Arg-7 of CTx ImI and Tyr-195 of alpha7 that anchors the toxin to the binding site. We also find multiple weak interactions between Asp-5 of CTx ImI and Trp-149, Tyr-151, and Gly-153 of alpha7, and between Trp-10 of CTx ImI and Thr-77 and Asn-111 of alpha7. The overall results establish the orientation of CTx ImI as it bridges the subunit interface and demonstrate close approach of residues on opposing faces of the alpha7 binding site.  (+info)

Acetylcholine and epibatidine binding to muscle acetylcholine receptors distinguish between concerted and uncoupled models. (6/410)

The muscle acetylcholine receptor (AChR) has served as a prototype for understanding allosteric mechanisms of neurotransmitter-gated ion channels. The phenomenon of cooperative agonist binding is described by the model of Monod et al. (Monod, J., Wyman, J., and Changeux, J. P. (1965) J. Mol. Biol. 12, 88-118; MWC model), which requires concerted switching of the two binding sites between low and high affinity states. The present study examines binding of acetylcholine (ACh) and epibatidine, agonists with opposite selectivity for the two binding sites of mouse muscle AChRs. We expressed either fetal or adult AChRs in 293 HEK cells and measured agonist binding by competition against the initial rate of 125I-alpha-bungarotoxin binding. We fit predictions of the MWC model to epibatidine and ACh binding data simultaneously, taking as constants previously determined parameters for agonist binding and channel gating steps, and varying the agonist-independent parameters. We find that the MWC model describes the apparent dissociation constants for both agonists but predicts Hill coefficients that are far too steep. An Uncoupled model, which relaxes the requirement of concerted state transitions, accurately describes binding of both ACh and epibatidine and provides parameters for agonist-independent steps consistent with known aspects of AChR function.  (+info)

The block of Shaker K+ channels by kappa-conotoxin PVIIA is state dependent. (7/410)

kappa-conotoxin PVIIA is the first conotoxin known to interact with voltage-gated potassium channels by inhibiting Shaker-mediated currents. We studied the mechanism of inhibition and concluded that PVIIA blocks the ion pore with a 1:1 stoichiometry and that binding to open or closed channels is very different. Open-channel properties are revealed by relaxations of partial block during step depolarizations, whereas double-pulse protocols characterize the slower reequilibration of closed-channel binding. In 2.5 mM-[K+]o, the IC50 rises from a tonic value of approximately 50 to approximately 200 nM during openings at 0 mV, and it increases e-fold for about every 40-mV increase in voltage. The change involves mainly the voltage dependence and a 20-fold increase at 0 mV of the rate of PVIIA dissociation, but also a fivefold increase of the association rate. PVIIA binding to Shaker Delta6-46 channels lacking N-type inactivation or to wild phenotypes appears similar, but inactivation partially protects the latter from open-channel unblock. Raising [K+]o to 115 mM has little effect on open-channel binding, but increases almost 10-fold the tonic IC50 of PVIIA due to a decrease by the same factor of the toxin rate of association to closed channels. In analogy with charybdotoxin block, we attribute the acceleration of PVIIA dissociation from open channels to the voltage-dependent occupancy by K+ ions of a site at the outer end of the conducting pore. We also argue that the occupancy of this site by external cations antagonizes on binding to closed channels, whereas the apparent competition disappears in open channels if the competing cation can move along the pore. It is concluded that PVIIA can also be a valuable tool for probing the state of ion permeation inside the pore.  (+info)

A marine snail neurotoxin shares with scorpion toxins a convergent mechanism of blockade on the pore of voltage-gated K channels. (8/410)

kappa-Conotoxin-PVIIA (kappa-PVIIA) belongs to a family of peptides derived from a hunting marine snail that targets to a wide variety of ion channels and receptors. kappa-PVIIA is a small, structurally constrained, 27-residue peptide that inhibits voltage-gated K channels. Three disulfide bonds shape a characteristic four-loop folding. The spatial localization of positively charged residues in kappa-PVIIA exhibits strong structural mimicry to that of charybdotoxin, a scorpion toxin that occludes the pore of K channels. We studied the mechanism by which this peptide inhibits Shaker K channels expressed in Xenopus oocytes with the N-type inactivation removed. Chronically applied to whole oocytes or outside-out patches, kappa-PVIIA inhibition appears as a voltage-dependent relaxation in response to the depolarizing pulse used to activate the channels. At any applied voltage, the relaxation rate depended linearly on the toxin concentration, indicating a bimolecular stoichiometry. Time constants and voltage dependence of the current relaxation produced by chronic applications agreed with that of rapid applications to open channels. Effective valence of the voltage dependence, zdelta, is approximately 0.55 and resides primarily in the rate of dissociation from the channel, while the association rate is voltage independent with a magnitude of 10(7)-10(8) M-1 s-1, consistent with diffusion-limited binding. Compatible with a purely competitive interaction for a site in the external vestibule, tetraethylammonium, a well-known K-pore blocker, reduced kappa-PVIIA's association rate only. Removal of internal K+ reduced, but did not eliminate, the effective valence of the toxin dissociation rate to a value <0.3. This trans-pore effect suggests that: (a) as in the alpha-KTx, a positively charged side chain, possibly a Lys, interacts electrostatically with ions residing inside the Shaker pore, and (b) a part of the toxin occupies an externally accessible K+ binding site, decreasing the degree of pore occupancy by permeant ions. We conclude that, although evolutionarily distant to scorpion toxins, kappa-PVIIA shares with them a remarkably similar mechanism of inhibition of K channels.  (+info)

α-Conotoxins isolated from Conus venoms contain 11-19 residues and preferentially fold into the globular conformation that possesses a specific disulfide pairing pattern (C1-3, C2-4). We and others isolated a new family of χ-conotoxins (also called λ conotoxins) with the conserved cysteine framework of α-conotoxins but with alternative disulfide pairing (C1-4, C2-3) resulting in the ribbon conformation. In both families, disulfide pairing and hence folding are important for their biological potency. By comparing the structural differences, we identified potential structural determinants responsible for the folding tendencies of these conotoxins. We examined the role of conserved proline in the first intercysteine loop and the conserved C-terminal amide on folding patterns of synthetic analogues of ImI conotoxin by comparing the isoforms with the regiospecifically synthesized conformers. Deamidation at the C-terminus and substitution of proline in the first intercysteine loop switch the ...
Marine drugs have developed rapidly in recent decades. Cone snails, a group of more than 700 species, have always been one of the focuses for new drug discovery. These venomous snails capture prey using a diverse array of unique bioactive neurotoxins, usually named as conotoxins or conopeptides. These conotoxins have proven to be valuable pharmacological probes and potential drugs due to their high specificity and affinity to ion channels, receptors, and transporters in the nervous systems of target prey and humans. Several research groups, including ours, have examined the venom gland of cone snails using a combination of transcriptomic and proteomic sequencing, and revealed the existence of hundreds of conotoxin transcripts and thousands of conopeptides in each Conus species. Over 2000 nucleotide and 8000 peptide sequences of conotoxins have been published, and the number is still increasing quickly. However, more than 98% of these sequences still lack 3D structural and functional information. With
Highly selective N-type voltage-gated calcium (CaV) channel inhibitors from cone snail venom (the ω-conotoxins) have emerged as a new class of therapeutics for the treatment of chronic and neuropathic pain. Earlier in 2005, Prialt (Elan) or synthetic ω-conotoxin MVIIA, was the first ω-conotoxin to be approved by Food and Drug Administration for human use. This review compares the action of three ω-conotoxins, GVIA, MVIIA and CVID, describing their structure-activity relationships and potential as leads for the design of improved N-type therapeutics that are more useful in the treatment of chronic pain.
Conotoxins (conopeptides) are a diverse group of peptides isolated from the venom of marine cone snails. Conus peptides modulate pain by interacting with voltage-gated ion channels and G protein-coupled receptors (GPCRs). Opiate drugs targeting GPCRs have long been used, nonetheless, many undesirable side effects associated with opiates have been observed including addiction. Consequently, alternative avenues to pain management are a largely unmet need. It has been shown that various voltage-gated calcium channels (VGCCs) respond to GPCR modulation. Thus, regulation of VGCCs by GPCRs has become a valuable alternative in the management of pain. In this review, we focus on analgesic conotoxins that exert their effects via GPCR-mediated inhibition of ion channels involved in nociception and pain transmission. Specifically, α-conotoxin Vc1.1 activation of GABAB receptors and inhibition of voltage-gated calcium channels as a novel mechanism for reducing the excitability of dorsal root ganglion neurons is
α-Conotoxins Vc1.1 and RgIA are small peptides isolated from the venom of marine cone snails. They have effective anti-nociceptive actions in rat models of neuropathic pain. Pharmacological studies in rodent dorsal root ganglion (DRG) show their analgesic effect is mediated by inhibition of N-type (Cav2.2) calcium channels via a pathway involving γ-aminobutyric acid type B (GABAB) receptor. However, there is no direct demonstration that functional GABAB receptors are needed for inhibition of the Cav2.2 channel by analgesic α-conotoxins. This study examined the effect of the GABAB agonist baclofen and α-conotoxins Vc1.1 and RgIA on calcium channel currents after transient knockdown of the GABAB receptor using RNA interference. Isolated rat DRG neurons were transfected with small interfering RNAs (siRNA) targeting GABAB subunits R1 and R2. Efficient knockdown of GABAB receptor expression at mRNA and protein levels was confirmed by quantitative real time PCR (qRT-PCR) and immunocytochemical analysis,
Designing novel conotoxins with therapeutic potential Conotoxins, with their exquisite specificity and potency have recently created much excitement as drug leads for the treatment of chronic pain. For example, the conotoxin MVIIA (also known as Ziconotide or Prialt) has been approved for use in the U.S. and Europe for the treatment of pain and several other conotoxins have entered clinical trials. In addition, a number of conotoxins have played a critical role in dissecting the molecular mechanisms of ion channel and transporter functions in the nervous system.. There are projects available in the design of novel conotoxins that target specific receptors involved in pain.. ...
1G1P: NMR Solution Structures of delta-Conotoxin EVIA from Conus ermineus That Selectively Acts on Vertebrate Neuronal Na+ Channels.
by Justin A. Varholick Ph.D., University of Florida, Department of Biology and UF Genetics Institute Too often we read about new research using mice, rats, non-human primates, and fish. These few categories of animals teach us a lot about biology and how we may intervene to cure or alleviate a human disease. But, what about…
Disulfide-rich neurotoxins from venomous animals continue to provide compounds with therapeutic potential. Minimizing neurotoxins often results in removal of disulfide bridges or critical amino acids. To address this drug-design challenge, we explored the concept of disulfide-rich scaffolds consisting of isostere polymers and peptidic pharmacophores. Flexible spacers, such as amino-3-oxapentanoic or 6-aminohexanoic acids, were used to replace conformationally constrained parts of a three-disulfide-bridged conotoxin, SIIIA. The peptide-polymer hybrids, polytides, were designed based on cladistic identification of nonconserved loci in related peptides. After oxidative folding, the polytides appeared to be better inhibitors of sodium currents in dorsal root ganglia and sciatic nerves in mice. Moreover, the polytides appeared to be significantly more potent and longer-lasting analgesics in the inflammatory pain model in mice, when compared to SIIIA. The resulting polytides provide a promising ...
As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
K+ channel of 529 aas and 6 TMSs, Kv1.6 or KCNA6. It can form functional homotetrameric channels and heterotetrameric channels that contain variable proportions of KCNA1, KCNA2, KCNA4, KCNA6, and possibly other family members (). channel properties depend on the type of alpha subunits that are part of the channel. Channel properties are modulated by cytoplasmic beta subunits that regulate the subcellular location of the alpha subunits and promote rapid inactivation (By similarity). Homotetrameric channels display rapid activation and slow inactivation (Grupe et al. 1990). It is inhibited by 0.6 μM β-defensin 3 (BD3) (Zhang et al. 2018) as well as by neurotoxic cone snail peptide μ-GIIIA and other conotoxins (Leipold et al. 2017 ...
CONICET Digital, el repositorio institucional del CONICET, un servicio gratuito para acceder a la producción científico-tecnológica de investigadores, becarios y demás personal del CONICET.
http://onlinelibrary.wiley.com/doi/10.1002/anie.201000620/abstract The Engineering of an Orally Active Conotoxin for the Treatment of Neuropathic Pain...
Voltage-gated Na+ channels are involved in the generation of action potentials in excitable cells. Structural determinants of major physiological characteristics (i.e., ion selectivity, gating, and ligand binding) are localized in the α subunit (Catterall, 2000; Hille, 2001). It is composed of four homologous domains (I-IV) quasi-symmetrically arranged around the central pore (Sato et al., 2001). Each domain contains six transmembrane segments (S1-S6), a pore-forming region (P), and the intracellular N and C ends (Guy and Seetharamulu, 1986; Denac et al., 2000). The P region contains the selectivity filter formed by a circular motif of highly conserved Asp, Glu, Lys, and Ala residues called the DEKA locus (Terlau et al., 1991; Heinemann et al., 1992). The selectivity filter separates the outer pore, which is targeted by tetrodotoxin (TTX), saxotoxin, and conotoxins, from the inner pore, which is targeted by local anesthetics (LAs) and other small cationic drugs (Zhorov and Tikhonov, 2004). Na+ ...
Raffaella G., Sole,C., Llecha,N, Segura, M.F., Moubarak,R., Iglesias-Guimarais,V., Perez-Garcia,M.J., Reix,S., Zhang,J., Badiola,N., Sanchis,D., Rodriguez-Alvarez,J.,Trullas,R., Yuste,V.J., and J.X. Comella ...
Analizar y valorar, en la rata como modelo animal de neurodegeneración, posibles mecanismos inflamatorios involucrados en la toxicidad del péptido Aβ. Así como mecanismos por los que el calcio participa en la activación de astrocitos en fases tempranas (24h - 2 semanas) de la toxicidad inducida por el péptido Aβ1-42. ...
Am vazut emisiunea lui Maruta si sunt impresionata de evolutia voastra, a fratilor Traistariu! Sunteti cu totii niste artisti, fiecare in arta lui. Parintii vostri de acolo de unde sunt, va lumineaza drumul cu dragoste si cu siguranta sunt mandrii ca voi sunteti cu totii si fiecare in parte niste copii atat de minunati. Imi plac tablourile tale Vasile, dar nu imi este clar cum pot sa le cumpar?! Imi plac absolut toate, si imi doresc sa imi impodobesc micuta mea casa cu cateva dintre ele...caci simt energia lor benefica...Astept un semn in acest sens pe adresa mea de email pe care am lasat-o. Dumnezeu sa va ocroteasca sa fiti cu sufletul mereu impreuna...viata asta materiala, vine si pleaca...voi existati prin simtul vostru artistic. Va doresc din tot sufletul sa fiti de sfintele sarbatori de Paste impreuna asa cum imi doresc si pentru familia mea (eu am trei copii minunati si extraordinari ca si voi) si pentru toti cei care pe lumea asta inteleg ca ne-am nascut sa ne iubim neconditionat ...
A peptide contained in the venom of the predatory marine snail Conus tulipa, rho-TIA, has previously been shown to possess alpha1-adrenoreceptor antagonist activity. Here, we further characterize its pharmacological activity as well as its structure-activity relationships. In the isolated rat vas deferens, rho-TIA inhibited alpha1-adrenoreceptor-mediated increases in cytosolic Ca2+ concentration that were triggered by norepinephrine, but did not affect presynaptic alpha2-adrenoreceptor-mediated responses. In radioligand binding assays using [125I]HEAT, rho-TIA displayed slightly greater potency at the alpha 1B than at the alpha 1A or alpha 1D subtypes. Moreover, although it did not affect the rate of association for [3H]prazosin binding to the alpha 1B-adrenoreceptor, the dissociation rate was increased, indicating non-competitive antagonism by rho-TIA. N-terminally truncated analogs of rho-TIA were less active than the full-length peptide, with a large decline in activity observed upon removal ...
Marine snails form the dominant component of molluscan faunas throughout the worlds oceans. There are about 600 different species of cone snails found distributed in warm and tropical seas and oceans worldwide, and the greatest diversity is seen in the Western Indo-Pacific Region. Cone snail venoms such as conotoxins and conopeptides show great promise as a source of new and medically important substances. The synthetic version of the conopeptide called ziconotide has been approved as a medication in the United States by the FDA (Food and Drug Administration) and is in current use as an analgesic (pain reliever). Conantokins, which are a family of conopeptides found in cone snail venom, serve as sleeper peptides, and these peptides work by a mechanism that may be helpful for people with epilepsy ...
Kaas Q, Westermann JC, Halai R, Wang CK and Craik DJ. ConoServer, a database for conopeptide sequences and structures. Bioinformatics (2008) 24(3):445-6 ConoServer is managed at the Institute of Molecular Bioscience IMB, Brisbane, Australia. The database and computational tools found on this website may be used for academic research only, provided that it is referred to ConoServer, the database of conotoxins (http://www.conoserver.org) and the above reference is cited. For any other use please contact David Craik ([email protected]). ...
Kaas Q, Westermann JC, Halai R, Wang CK and Craik DJ. ConoServer, a database for conopeptide sequences and structures. Bioinformatics (2008) 24(3):445-6 ConoServer is managed at the Institute of Molecular Bioscience IMB, Brisbane, Australia. The database and computational tools found on this website may be used for academic research only, provided that it is referred to ConoServer, the database of conotoxins (http://www.conoserver.org) and the above reference is cited. For any other use please contact David Craik ([email protected]). ...
During evolution, nature has embraced different strategies for species to survive. One strategy, applied by predators as diverse as snakes, scorpions, sea anemones and cone snails, is using venom to immobilize or kill a prey. This venom offers a unique and extensive source of chemical diversity as it is driven by the evolutionary pressure to improve prey capture and/or to protect their species. Cone snail venom is an example of the remarkable diversity in pharmacologically active small peptides that venoms can consist of. These venom peptides, called conopeptides, are classified into two main groups based on the number of cysteine residues, namely disulfide-rich and disulfide-poor conopeptides. Since disulfide-poor conotoxins are minor components of this venom cocktail, the number of identified peptides and the characterization of these peptides is far outclassed by its cysteine-rich equivalents. This review provides an overview of 12 families of disulfide-poor peptides identified to date as well as the
With more than 2600 studies published in the last 20 years, there is much excitement about conotoxins in biomedicine. Most conotoxins are a succinct ten to forty amino acids in length and are exquisitely selective about their receptor binding sites. This makes them powerful tools for understanding how cells work and a rich source for discovery of new medicines, said Bernstein. Among many discoveries, conotoxins that block key neurological pathways have been effective in the early detection and may also help treat small-cell lung cancer, one of the most devastating human cancers. A compound now in clinical trials has powerful anti-epileptic activity. Experiments suggest that conotoxins could treat muscle spasticity following spinal cord injury. They could prevent cell death when there is inadequate circulation, such as during strokes, head injuries or coronary bypass surgery. They could also be used to treat clinical depression, heart arrhythmias and urinary incontinence ...
Biggs J.S., Watkins M., Puillandre N., Ownby J.P., Lopez-Vera E., Christensen S., Moreno K.J., Bernaldez J., Licea-Navarro A., Corneli P.S., Olivera B.M.. Conus species are characterized by their hyperdiverse toxins, encoded by a few gene superfamilies. Our phylogenies of the genus, based on mitochondrial genes, confirm previous results that C. californicus is highly divergent from all other species. Genetic and biochemical analysis of their venom peptides comprise the fifteen most abundant conopeptides and over 50 mature cDNA transcripts from the venom duct. Although C. californicus venom retains many of the general properties of other Conus species, they share only half of the toxin gene superfamilies found in other Conus species. Thus, in these two lineages, approximately half of the rapidly diversifying gene superfamilies originated after an early Tertiary split. Such results demonstrate that, unlike endogenously acting gene families, these genes are likely to be significantly more ...
Conus geographus�Intro - Slide 1 (Cone shell snail)Ralph Waldo Emerson once stated The most dangerous thing is illusion. Good morning/afternoon ladies and gentlemen, my name is Tobias and today I will speak to you on the dangerous illusion tha...
Cone shells (Conidae) are a group of predatory marine snails. This group has not yet been divided into various genera, so that all of the approximately 300 species are included in the genus Conus.. Cone shells, like their close relatives the Turrids (Turridae), Mitre shells (Mitridae), Cytharidae and Auger shells (Terebridae), have developed an unusual venom apparatus for catching prey. However, only Cone shells are known to have caused envenoming in humans.. The shell of the Conidae is in the form of a rolled cone. There is a slit-like opening on the long side through which the animals evert their foot. The larger species, such as C. geographus, reach a length of up to 15 cm. With their often strikingly beautifully patterned shells, Cone shells are highly prized among shell collectors.. Cone shells live in shallow water, including coastal zones, especially reef areas, where they conceal themselves in crevices or bury themselves in the sand during the day. Only at dusk do they start appearing ...
The GluN2B subunit of the N-methyl-d-aspartate receptor (NMDAr) modulates many physiological processes including learning, memory, and pain. Excessive increase in NMDAr/GluN2B activity has been associated with various disorders such neuropathic pain and neuronal death following hypoxia. Thus there is an interest in identifying NMDAr antagonists that interact specifically with the GluN2B subunit. Recently based on structural analysis between the GluN2B subunit and conantokin-G, a toxin that interacts selectively with the GluN2B subunit, we designed various peptides that are predicted to act as NMDAr antagonists by interacting with the GluN2B subunit. In this study we tested this prediction for two of these peptides EAR16 and EAR18. The effects of EAR16 and EAR18 in NMDA-evoked currents were measured in cultured rat embryonic hippocampal neurons and in HEK-293 cells expressing recombinant NMDAr comprised of GluN1a-GluN2A or GluN1a-GluN2B subunits. In hippocampal neurons, EAR16 and EAR18 reduced the NMDA
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Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them.
TY - JOUR. T1 - Identification of residues in the neuronal α7 acetylcholine receptor that confer selectivity for conotoxin ImI. AU - Quiram, Polly A.. AU - Sine, Steven M.. PY - 1998/5/1. Y1 - 1998/5/1. N2 - To identify residues in the neuronal α7 acetylcholine subunit that confer high affinity for the neuronal-specific toxin conotoxin ImI (CTx ImI), we constructed α7-α1 chimeras containing segments of the muscle α1 subunit inserted into equivalent positions of the neuronal α7 subunit. To achieve high expression in 293 human embryonic kidney cells and formation of homo-oligomers, we joined the extracellular domains of each chimera to the M1 junction of the 5-hydroxytryptamine-3 (5HT-3) subunit. Measurements of CTx ImI binding to the chimeric receptors reveal three pairs of residues in equivalent positions of the primary sequence that confer high affinity of CTx ImI for α7/5HT-3 over α1/5HT-3 homo-oligomers. Two of these pairs, α7Trp55/α1Arg55 and α7Ser59/α1Gln59, are within one of ...
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The Childrens Tumor Foundation is one of IMIs Associated Partners. Annette Bakker, the Foundations president, says that the unique IMI model ensures alignment between industry and public partners.
The Conus genus includes around 500 species of marine mollusks using a peculiar production of venomous peptides referred to as conotoxins (CTX). S1) living generally in the tropical marine areas. About 700 species of Cone snails express hundreds of peptide toxins collectively known as conotoxins (CTX) aimed to self-defense, competition and predation of other marine species by means of stingCstructures that were reported to be fatal for human since from 300 years ago. CTX, however, do not exert only venomous activity but have a lot of pharmacological properties with specific bioactivity in the treatment of neurological disorders and the associated pain belief [1,2,3]. The presence of disulfide bonds is the important characteristic for natural function of CTX that enable to separate CTX into two primary types, the disulfide-rich peptides and no-disulfide-rich types; the foremost is generally composed of no more than 30 proteins and the next contains as much as 80 proteins. CTX are grouped into ...
Subunit non-selective N-methyl-D-aspartate (NMDA) receptor antagonists reduce injury-induced pain behavior, but generally produce unacceptable side effects. In this study, we examined the antinociceptive and motor effects of cone snail venom-derived peptides, conantokins G and T (conG and conT), whi …
Cone snails use their venom to paralyze their prey. Although the venom is often dangerous for humans, it contains chemicals that may have important medical benefits.
With the use of ultra-high-speed videography, Ecology and Evolutionary Biology Associate Professor Emanuel Azizi and colleagues from Occidental College Los Angeles have shed light on the hunting mechanism of the cone snail Conus catus. Published online in Current Biology - Cell Press, the researchers identified the snails hydraulically propelled feeding structure as the quickest movement among mollusks by an order of magnitude.
But beware! Cone Snails have a extremely potent toxin (called Conotoxin), and they have to. They are tiny little guys who dont move very fast. Their toxin needs to paralyze their prey quickly, otherwise itll get away. The toxin in these Snails has the ability to kill a human being, and there is no known antivenom. They attack via a barb that shoots out from their shell, and the type of paralysis is dependent on the species. When their prey is immobilized, they draw it back in to their shell, still attached to the barb. Cone Snails are carnivorous and predatory, and feed off of fish, worms, and other mollusks, depending on the specific species ...
Tiny marine snails known as sea butterflies appear to fly underwater much like winged insects do when taking to the sky - representsing a remarkable example of convergent evolution, where two unrelated species develop features that are used in similar ways.
While considered a delicacy in some parts of the world, snails have found a more intriguing use to scientists and the medical profession offering a plethora of research possibilities.
Research Interests:. Foldamers are unnatural oligomers with a propensity to adopt well-defined conformations. These molecules have seen success in the mimicry of canonical peptide secondary structures such as -helices and -sheets. Current efforts in the field involve the application of foldamer design strategies to mimic higher-order protein structures and novel peptide architectures. Disulfide-rich peptides are notable candidates for foldamer research due to their intricate folding patterns and potent bioactivities. I am interested in establishing foldamer design principles for the synthesis of disulfide-rich peptide analogs with heterogeneous backbone modifications that manifest specific conformations, desired functionality and improved pharmacological properties.. Education:. B.S. in Microbiology, University of Hawaii at Manoa, 2008. M.S. in Molecular Biosciences and Bioengineering, University of Hawaii at Manoa, 2014. ...
The big problems with morphine are addictiveness and the fact that people develop a tolerance to it, says Professor David Adams, director of the RMIT Health Innovations Research Institute. With the painkillers derived from cone snail venom, we dont have those problems. People dont develop tolerance, and they dont get hooked.. Also, theres a wide safety margin. With morphine, theres little room for error. If you overdose, youre likely to die. But with the venom peptides, there may be side-effects but you will survive.. David leads research into the cocktail of peptides-fragments of protein-with which the cone snail paralyses its prey. These peptides have exquisite selectivity for their molecular targets, he says. So his team is geared to developing new treatments for chronic nerve-based pain by discovering and purifying peptides that target particular pain receptors.. Worldwide, there are more than 700 species of cone snails, about two-thirds of which are found in the Great Barrier ...
TY - JOUR. T1 - The Single Disulfide-Directed β-Hairpin Fold. Dynamics, Stability, and Engineering. AU - Chittoor, Balasubramanyam. AU - Krishnarjuna, Bankala. AU - Morales, Rodrigo A.V.. AU - Macraild, Christopher A.. AU - Sadek, Maiada M.. AU - Leung, Eleanor W.W.. AU - Robinson, Samuel D.. AU - Pennington, Michael William. AU - Norton, Raymond S.. PY - 2017/5/16. Y1 - 2017/5/16. N2 - Grafting bioactive peptide sequences onto small cysteine-rich scaffolds is a promising strategy for enhancing their stability and value as novel peptide-based therapeutics. However, correctly folded disulfide-rich peptides can be challenging to produce by either recombinant or synthetic means. The single disulfide-directed β-hairpin (SDH) fold, first observed in contryphan-Vc1, provides a potential alternative to complex disulfide-rich scaffolds. We have undertaken recombinant production of full-length contryphan-Vc1 (rCon-Vc1[Z1Q]) and a truncated analogue (rCon-Vc11-22[Z1Q]), analyzed the backbone dynamics of ...
Coniine,(2S)-2-Propylpiperidine,cicutine,conicine,Hydrobromide,Coniine Hydrobromide,Hydrochloride,Coniine Hydrochloride,(R)-(-)-Form,(R)-(-)-Coniine,(+/-)-Form,(+/-)-Coniine
Wilson, David, Bansal, Paramjit S., Carter, David A., Vetter, Irina, Nicke, Annette, Dutertre, Sébastien, and Daly, Norelle (2020) Characterisation of a novel A-superfamily conotoxin. Biomedicines, 8 (5). 128. Takjoo, Rozita, Wilson, David T., Bansal, Paramjit, Loukas, Alex, Smout, Michael J., and Daly, Norelle L. (2020) Folding of truncated granulin peptides. Biomolecules, 10 (8). 1152. Schmidt, Casey A., Wilson, David T., Cooke, Ira, Potriquet, Jeremy, Tungatt, Katie, Muruganandah, Visai, Boote, Chloe, Kuek, Felicity, Miles, John J., Kupz, Andreas, Ryan, Stephanie, Loukas, Alex, Bansal, Paramjit S., Takjoo, Rozita, Miller, David J., Peigneur, Steve, Tytgat, Jan, and Daly, Norelle (2020) Identification and characterization of a peptide from the stony coral Heliofungia actiniformis. Journal of Natural Products, 83 (11). pp. 3454-3463. Dastpeyman, Mohadeseh, Giacomin, Paul, Wilson, David, Nolan, Matthew J., Bansal, Paramjit S., and Daly, Norelle L. (2019) A C-terminal fragment of chlorotoxin ...
Castro J, Grundy L, Deiteren A, Harrington AM, ODonnell T, Maddern J, Moore J, Garcia-Caraballo S, Rychkov GY, Yu R, Kaas Q, Craik DJ, Adams DJ, Brierley ...
InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites. We combine protein signatures from a number of member databases into a single searchable resource, capitalising on their individual strengths to produce a powerful integrated database and diagnostic tool.
IMI held its IMI 2 Open Info Day in Brussels on Tuesday 30 September 2014. The event was well-attended, with more than 290 people participating either in person or remotely via the webcast. On top of a review of the new IMI 2 rules and Call procedures, IMIs founding partners presented their perspectives on IMI 2. In the afternoon, there were two topic-related workshops on the IMI 2 Call 1 topics, as well as plenty of networking opportunities throughout the day. During the workshops, participants were invited to make an elevator pitch or short presentation to the other participants about their organisation. The final session gave a preview of whats coming later this year in IMIs second IMI 2 Call, giving participants the chance to ask three of the topic writers directly about the new indicative topics.. The whole days events were recorded and the videos of each session will be viewable on IMIs YouTube channel.. ...
The first Part is atmospheric, dense and more progressive. The second part (my favorite) is also atmospheric, dense with some guttural vocals and painful chants, and the best ultra-slow riffs, sometimes almost Funeral Doom (anybody says Evoken ...
The Merck Index* Online | Coniine | Monograph containing literature references, physical and biological properties and relevant information
Premiul va rasplati descrierea care ma va convinge si pe mine ca imi cunosti blogul. Atentie nu trebuie nici sa ma lauzi, nici sa ma faci praf, eu nu sunt fana a extremelor, adica daca imi citesti blogul te-ai cam lamurit despre ce scriu si cum scriu. Imi doresc sa imi spui simplu si in termeni normali ce reprezinta blogul meu pentru tine si cum i-ai spune tu rapid cuiva ceva despre blogul meu. Lasa-mi textul acesta in comentariu la acest articol. ...
Conotoxins[edit]. Ziconotide is a voltage-gated calcium channel blocker which may be used in severe cases of ongoing ...
Daly NL, Craik DJ (February 2009). "Structural studies of conotoxins". IUBMB Life. 61 (2): 144-50. doi:10.1002/iub.158. PMID ... Such proteins include C1q, elastins, PrP, Argonaute 2, and conotoxins, among others. As prolyl hydroxylase requires ascorbate ...
All conorfamides are disulfide-poor conotoxins. CNF-Sr3 shares 73.3% sequence similarity with CNF-Sr1 and 31.0% sequence ...
Conotoxins represent a category of poisons produced by the marine cone snail, and are capable of inhibiting the activity of a ... One of the unique forms of conotoxins, ω-conotoxin (ω-CgTx) is highly specific for Ca channels and has shown usefulness in ... In many cases, the toxins released by the different types of cone snails include a range of different types of conotoxins, ... Jacob, Reed B.; McDougal, Owen M. (2010). "The M-superfamily of Conotoxins: a Review". Cellular and Molecular Life Sciences. 67 ...
The conotoxins contain target specificity and short sequences. An example of this phenomenon is ω-MVIIA which targets Ca2+ ... Gao B, Peng C, Yang J, Yi Y, Zhang J, Shi Q (December 2017). "Cone Snails: A Big Store of Conotoxins for Novel Drug Discovery ... The toxins in these various venoms are called conotoxins. These are various peptides, each targeting a specific nerve channel ... Natural History Museum Rotterdam - photos of Conus shells Cone snail and conotoxins page The Conus Biodiversity website ...
These toxins are known as conotoxins or conopeptides. The toxins are of importance to medical research. A notable feature of ...
Their venom contains conotoxins which have powerful neurotoxic effects. Given that they are capable of "stinging" humans, live ...
Buczek O, Bulaj G, Olivera BM (December 2005). "Conotoxins and the posttranslational modification of secreted gene products". ...
Mu-conotoxins have two types of cysteine arrangements, but the knottin scaffold is not observed. Mu-conotoxins target the ... whereas delta conotoxins delay the inactivation of sodium channels, and kappa conotoxins are potassium channel blockers. ... The number of conotoxins whose activities have been determined so far is five, and they are called the α(alpha)-, δ(delta)-, κ( ... Conotoxins have a variety of mechanisms of actions, most of which have not been determined. However, it appears that many of ...
N-type-selective: ω-Conotoxins. *ω-Conotoxin GVIA. *Caroverine. *Huwentoxin XVI. *Leconotide (ω-conotoxin CVID) ...
N-type-selective: ω-Conotoxins. *ω-Conotoxin GVIA. *Caroverine. *Huwentoxin XVI. *Leconotide (ω-conotoxin CVID) ...
N-type-selective: ω-Conotoxins. *ω-Conotoxin GVIA. *Caroverine. *Huwentoxin XVI. *Leconotide (ω-conotoxin CVID) ...
ω-Conotoxins are derived from the venom of cone snails. ω-Conotoxin MVIIC acts within the hippocampal CA1 pyramidal neurons to ...
"Therapeutic applications of conotoxins that target the neuronal nicotinic acetylcholine receptor". Toxicon. 48 (7): 810-29. doi ...
The Conus Biodiversity website Cone Shell and Conotoxins website Pain Killer Comes out of its Shell - The Age 25 July 2005 ... "Therapeutic applications of conotoxins that target the neuronal nicotinic acetylcholine receptor". Toxicon. 48 (7): 810-29. doi ...
... neosaxitoxin and several of the conotoxins also bind the same site. The use of this toxin as a biochemical probe has elucidated ...
Some snail poisons, conotoxins, contain hydroxyproline, but lack collagen-like sequences. Hydroxylation of proline has been ...
Biodiversity-Derived Discovery of Novel Sodium Channel Blocking Conotoxins from Conus bullatus". Toxicon. 53 (1): 90-8. doi: ...
"The alpha2delta auxiliary subunit reduces affinity of omega-conotoxins for recombinant N-type (Cav2.2) calcium channels". The ...
These molecules, called conotoxins, led to a breakthrough in the study of ion channels and neuromuscular synapses. He ... His impressive research on both DNA biophysics and conotoxins has enabled Dr Olivera to serve as an editorial board member of ...
HWTX-X has selectivity for isoforms of N-type Ca2+ channels, compared with ω-conotoxins GVIA and MVIIA. HWTX-X specifically ... While structurally similar to ω-conotoxins that block the twitch response to electrical nerve stimulation, HWTX-X has no effect ...
The Waglerins and complementary conotoxins are useful tools to discover the contribution of acetylcholine receptor subunits to ... "Definition and Characterization of the Short alphaA-Conotoxins: A Single Residue Determines Dissociation Kinetics from the ...
Although many N-type calcium channels blockers are known, most potent and selective belong to the family of conotoxins. List of ... a synthetic version of one of conotoxins A rare gain-of-function mutation in CACNA1B gene encoding the α1B subunit of N-type ... although the most notable blockers are ω-conotoxins. N-type calcium channels are categorized as high threshold-activated ... N-type Calcium channel blockers: ω-Conotoxins Cadmium Caroverine Cilnidipine Desipramine Gabapentin nonselectively inhibits N- ...
Her work focused on the isolation of peptides from the conotoxins in the snail's venom while their effects were still unknown. ... She has also contributed to the development of conotoxins as tools for examining the activity of the human brain. Her ... Her research shed light on the effects of conotoxins on the central nervous system and their connection to muscular paralysis, ... For example, two classes of conotoxins are used as analytical agents: ω-conotoxin has been widely used for studying neuronal ...
Since it has a structural similarity to the ω-conotoxins, it is possible that their blocking mechanism is similar. MVIIA is a ... and N-termini The structure of Ptu1 is slightly homologous with the ω-conotoxins.: Geographus Venom IA (GVIA) and Mollusc Venom ...
... s typically lack disulfide bonds, in contrast to most families of conotoxins, which have an unusually high density of ...
They are relatively homologous to the calcium channel blockers omega-conotoxins from marine cone snails and belong to the four- ...
C. regius is known to have more different conotoxins than any other Cone sail species, its conotoxin it's potentially of ...
It is thought that the conotoxins in the venom of cone snails are able to completely relax this muscle so that the body can be ...
Zugasti-Cruz, A., Aguilar, M.B., Falcon, A., Olivera, B.M., & Heimer de la Cotera, E.P. (2008) Two new 4-cys conotoxins ( ...
We tested two alternative oxidation strategies to produce conotoxins α-GI and μ-PIIIA. The peptides were either reversibly ...
The mode of action of several conotoxins has been the subject of investigation, while for many others this remains unknown. ... This review aims to give an overview of the knowledge we have today on the molecular pharmacology of conotoxins specifically ... Conotoxins Targeting Nicotinic Acetylcholine Receptors: An Overview by Eline K. M. Lebbe. , Steve Peigneur. , Isuru Wijesekara ... The mode of action of several conotoxins has been the subject of investigation, while for many others this remains unknown. ...
Biotinylated derivatives of omega-conotoxins GVIA and MVIID: probes for neuronal calcium channels.. Haack JA1, Kinser P, ... The omega-conotoxins are small, disulfide-rich peptides which inhibit voltage-sensitive calcium channels. Biotinylated omega- ... We describe the preparation and characterization of biotinylated derivatives of two specific omega-conotoxins, GVIA and MVIID, ... conotoxins are potentially useful reagents for characterizing distinct subsets of calcium channels. ...
omega-Conotoxins: A family of structurally related neurotoxic peptides from mollusk venom that inhibit voltage-activated entry ... omega-Conotoxins. Subscribe to New Research on omega-Conotoxins A family of structurally related neurotoxic peptides from ... 03/01/2013 - "Omega-conotoxins as experimental tools and therapeutics in pain management.". 11/10/2000 - "omega-Conotoxins ... 02/01/2010 - "Neuronal (N)-type Ca(2+) channel-selective omega-conotoxins have emerged as potential new drugs for the treatment ...
These conotoxins have proven to be valuable pharmacological probes and potential drugs due to their high specificity and ... These venomous snails capture prey using a diverse array of unique bioactive neurotoxins, usually named as conotoxins or ... Over 2000 nucleotide and 8000 peptide sequences of conotoxins have been published, and the number is still increasing quickly. ... and nine more conotoxins are at various stages of preclinical or clinical evaluation. In short, the genus Conus, the big family ...
In this case, over 40 conotoxins are characterized based on only two LC-ESI-MS experiments in terms of mass, number of ... Sequencing and mass profiling highly modified conotoxins using global reduction/alkylation followed by mass spectrometry.. ...
We have reported previously that the alpha9alpha10 nicotinic acetylcholine receptor (nAChR) selective-conotoxins Vc1.1 and RgIA ... Alpha-conotoxins Vc1.1 and RgIA are peptides from the venom of marine Conus snails that are currently in development as a ... Alpha-conotoxins Vc1.1 and RgIA are peptides from the venom of marine Conus snails that are currently in development as a ... We have reported previously that the alpha9alpha10 nicotinic acetylcholine receptor (nAChR) selective-conotoxins Vc1.1 and RgIA ...
... ... ω-conotoxins, such MVIIA and CVID are effective in neuropathic pain models. CVID is reported to have a greater therapeutic ... All ω-conotoxins produced dose-dependent reduction in mechanical allodynia. They also produced side effects on the rotarod test ... Finally, the conotoxins all presynaptically inhibited excitatory synaptic neurotransmission into the dorsal horn and displayed ...
Another family of conotoxins, the α-conotoxins, are competitive antagonists of mammalian nicotinic acetylcholine receptors ( ... Surprisingly, however, α-conotoxins Vc1.1, RgIA and PeIA more potently inhibit N-type VGCC currents via a GABA B GPCR mechanism ... Structurally related ω-conotoxins bind directly to and selectively inhibit neuronal (N)-type voltage-gated calcium channels ( ... A series of newly discovered ω-conotoxins from Conus catus, including CVID-F, are potent and selective antagonists of N-type ...
Here we report the isolation of μ-conotoxins SIIIA and SIIIB by 125I-TIIIA-guided fractionation of milked Conus striatus venom ... in solution comprising a series of turns and anα-helical motif across residues 11-16 that is not found in larger μ-conotoxins. ... "μ-Conotoxins are small peptide inhibitors of muscle and neuronal tetrodotoxin (TTX)-sensitive voltage-gated sodium channels ( ... μ-Conotoxins are small peptide inhibitors of muscle and neuronal tetrodotoxin (TTX)-sensitive voltage-gated sodium channels ( ...
mu-Conotoxins as leads in the development of new analgesics. In: Molecules. 2010 ; Vol. 15, No. 4. pp. 2825 - 2844. ... Norton, RS 2010, mu-Conotoxins as leads in the development of new analgesics, Molecules, vol. 15, no. 4, pp. 2825 - 2844. ... mu-Conotoxins as leads in the development of new analgesics. / Norton, Raymond S. ... Norton, R. S. (2010). mu-Conotoxins as leads in the development of new analgesics. Molecules, 15(4), 2825 - 2844. https://doi. ...
Distinct disulfide isomers of u-conotoxins KIIIA and KIIIB block voltage-gated sodium channels. In: Biochemistry. 2012 ; Vol. ... Distinct disulfide isomers of u-conotoxins KIIIA and KIIIB block voltage-gated sodium channels. / Khoo, Keith K; Gupta, Kallol ... Distinct disulfide isomers of u-conotoxins KIIIA and KIIIB block voltage-gated sodium channels. Biochemistry. 2012;51(49):9826 ... N2 - In the preparation of synthetic conotoxins containing multiple disulfide bonds, oxidative folding can produce numerous ...
... also called λ conotoxins) with the conserved cysteine framework of α-conotoxins but with alternative disulfide pairing (C1-4, ... α-Conotoxins isolated from Conus venoms contain 11-19 residues and preferentially fold into the globular conformation that ... The findings are corroborated by reciprocal folding of CMrVIA χ/λ-conotoxins. Substitution of Lys-6 from the first ... Protein folding determinants: Structural features determining alternative disulfide pairing in α- and χ/λ-conotoxins. ...
Conotoxins[edit]. Ziconotide is a voltage-gated calcium channel blocker which may be used in severe cases of ongoing ...
Conus genus includes around 500 species of marine mollusks with a peculiar production of venomous peptides known as conotoxins ... µ-Conotoxins Modulating Sodium Currents in Pain Perception and Transmission. Elisabetta Tosti , Raffaele Boni , Alessandra ... Tosti, E.; Boni, R.; Gallo, A. µ-Conotoxins Modulating Sodium Currents in Pain Perception and Transmission: A Therapeutic ... Tosti, E.; Boni, R.; Gallo, A. µ-Conotoxins Modulating Sodium Currents in Pain Perception and Transmission: A Therapeutic ...
Conotoxins are disulfide-rich peptides, from the venoms of marine cone snails, which are of pharmaceutical interest because ... Chemically re-engineering conotoxins to give them a cyclic backbone has been used to engender them with improved ... NMR and protein structure in drug design: application to cyclotides and conotoxins ... including cyclotides and conotoxins. Cyclotides are head-to-tail cyclized proteins from plants that are exceptionally stable ...
Ziconotide is the first FDA-approved agent in a promising class of drugs called the conotoxins. Its release carried the ... Conotoxins I became acquainted with conotoxins in the Spring 2000 when teaching at the University in Florida. There I met Dr. ... Delta-conotoxins activate neuronal sodium channels and are highly toxic to non-mammalian animal systems, and thus may prove ... Kappa-conotoxins target the voltage-sensitive K ion channel and under investigation as a class of future cardiovascular and ...
Fingerprint Dive into the research topics of α-Conotoxins. Together they form a unique fingerprint. * Conotoxins Medicine & ... title = "α-Conotoxins",. abstract = "α-Conotoxins (α-CgTxs) are a family of Cys-enriched peptides found in several marine ... α-Conotoxins. / Arias, Hugo R.; Blanton, Michael P.. In: International Journal of Biochemistry and Cell Biology, Vol. 32, No. ... α-Conotoxins (α-CgTxs) are a family of Cys-enriched peptides found in several marine snails from the genus Conus. These small ...
Disulfide bond assignments by mass spectrometry of native natural peptides: cysteine pairing in disulfide bonded conotoxins. ... Disulfide bond assignments by mass spectrometry of native natural peptides: cysteine pairing in disulfide bonded conotoxins. ... Disulfide bond assignments by mass spectrometry of native natural peptides: cysteine pairing in disulfide bonded conotoxins ( ...
N-type-selective: ω-Conotoxins. *ω-Conotoxin GVIA. *Caroverine. *Huwentoxin XVI. *Leconotide (ω-conotoxin CVID) ...
Abrin; conotoxins; diacetoxyscirpenol; ricin; saxitoxin; Shiga-like ribosome inactivating proteins; tetrodotoxin Exclusions: ¶ ... 100 mg of conotoxins; 1,000 mg of diacetoxyscirpenol; 100 mg of ricin; 100 mg of saxitoxin; 100 mg of Shiga-like ribosome ...
CONOTOXINS. *Conotoxins (non-short, paralytic alpha conotoxins; effective 12-4-2012). Based upon available experimental ... The conotoxins that remain on the HHS list will be limited to the short, paralytic alpha conotoxins containing the following ... The short, paralytic alpha conotoxins containing the following amino acid sequence X1 CCX2 PACGX3 X4 X5 X 6 CX 7 will be ... Liu L, Chew G, Hawrot E, Chi C, Wang C. Two potent alpha3/5 conotoxins from piscivorous Conus achatinus. Acta Biochim Biophys ...
Conotoxins; Diacetoxyscirpenol; Diphtheria toxin; Grayanotoxin; mushroom toxins such as amanitins, gyromitrin, and orellanine; ...
Conotoxins. *Crimean-Congo hemorrhagic fever. *Diacetoxyscirpenol. *Eastern equine encephalitis virus. *Ebola virus ...
The M-superfamily of conotoxins: a review. Cell Mol Life Sci. 2010;67:17-27.CrossRefPubMedGoogle Scholar ... Structure-activity studies on alpha-conotoxins. Curr Pharm Des. 2011;17:4226-41.CrossRefPubMedGoogle Scholar ... α-Conotoxins (α-CTxs) are small (10-30 residue) peptides derived from the venom of predatory marine cone snails of the genus ...
What are conotoxins?. Venomous sea snails use conotoxins to immobilise and kill their prey. ... Photo: Conotoxins, found in sea snail venom, appear to provide long-lasting pain relief. (Supplied: University of Wollongong) ... But the conotoxins now in development would hopefully be administered orally.. External Link: Killer Cone Snails: National ... "The conotoxins that were working on, we have intellectual property protection on most of them, were looking for commercial ...
Precursors of Novel Gla-Containing Conotoxins Contain a Carboxy-Terminal Recognition Site That Directs γ-Carboxylation - , -. ... Conotoxins: Highly modified peptide toxins from marine snails.. 1999. (Apresenta o de Trabalho/Semin rio). ... Invited Lecture.Conotoxins: Highly modified peptide toxins from marine snails. 1999. (Semin rio). ... Palavras-chave: mass spectrometry; MALDI MS; Proteomics; Conotoxins; Locusta migratoria; cuticular proteins. Grande rea: Ci ...
Daly NL, Craik DJ (February 2009). "Structural studies of conotoxins". IUBMB Life. 61 (2): 144-50. doi:10.1002/iub.158. PMID ... Such proteins include C1q, elastins, PrP, Argonaute 2, and conotoxins, among others. As prolyl hydroxylase requires ascorbate ...
Conotoxins are bioactive peptides found in the venom that marine cone snails produce for prey capture and defense. They are ... Conotoxins are also active on human receptors (e.g., ion channels), which is of particular interest as they thus can be used as ... Conotoxins are bioactive peptides found in the venom that marine cone snails produce for prey capture and defense. They are ... Using conotoxins for new methods New analytical advances in the fields of venomics, proteomics and transcriptomics have led to ...
  • Biotinylated derivatives of omega-conotoxins GVIA and MVIID: probes for neuronal calcium channels. (nih.gov)
  • The omega-conotoxins are small, disulfide-rich peptides which inhibit voltage-sensitive calcium channels. (nih.gov)
  • Biotinylated omega-conotoxins are potentially useful reagents for characterizing distinct subsets of calcium channels. (nih.gov)
  • We describe the preparation and characterization of biotinylated derivatives of two specific omega-conotoxins, GVIA and MVIID, which bind different calcium channel subtypes. (nih.gov)
  • These results indicate that the vicinity of the Lys10 residue of omega-conotoxin MVIID may be more critical for binding to the receptor target site than regions around other amino groups in omega-conotoxins GVIA and MVIID. (nih.gov)
  • The omega-conotoxins (including Ziconotide) inhibit presynaptic voltage-gated calcium channels and thus neurotransmission across nerve synapses. (spineuniverse.com)
  • With the role of the omega-conotoxins in treating severe chronic pain, this class of biochemicals is also under investigation in the possible development of a drug to treat brain injury secondary to ischemic stroke and hypoxia where there is some evidence that Ca channel blockade may be therapeutic. (spineuniverse.com)
  • The cysteine arrangements are the same for omega, delta and kappa families, even though omega conotoxins are calcium channel blockers, whereas delta conotoxins delay the inactivation of sodium channels, and kappa conotoxins are potassium channel blockers. (rug.nl)
  • Calcium channel diversity and neurotransmitter release: the omega-conotoxins and omega-agatoxins. (springer.com)
  • We have reported previously that the alpha9alpha10 nicotinic acetylcholine receptor (nAChR) selective-conotoxins Vc1.1 and RgIA potently and selectively inhibit high voltage-activated (HVA) N-type calcium channel currents in dissociated neurons from rat dorsal root ganglia (DRG). (nih.gov)
  • On-resin strategy to label α-conotoxins: Cy5-RgIA, a potent α9α10 nicotinic acetylcholine receptor imaging probe: Markus Muttenthaler, Simon Nevin, Marco Inserra, Richard Lewis, David Adams, and Paul Alewood. (eurekalert.org)
  • Alpha conotoxins have two types of cysteine arrangements, [16] and are competitive nicotinic acetylcholine receptor antagonists. (rug.nl)
  • and alpha-conotoxins - nicotinic acetylcholine receptor. (europa.eu)
  • Alpha-conotoxins Vc1.1 and RgIA are peptides from the venom of marine Conus snails that are currently in development as a treatment for neuropathic pain. (nih.gov)
  • α-Conotoxins Vc1.1 and RgIA possess two disulfide bonds and are currently in development as a treatment for neuropathic pain. (edu.au)
  • Results show that GABA(B) receptors R1 and R2 must be activated for the modulation of N-type (Ca(v)2.2) calcium channels by analgesic alpha-conotoxins Vc1.1 and RgIA. (antibodies-online.com)
  • The Conus genus includes around 500 species of marine mollusks with a peculiar production of venomous peptides known as conotoxins (CTX). (preprints.org)
  • The chemicals are known as conotoxins and up until now it has been hard to administer the right dose without causing bad side effects. (abc.net.au)
  • This venom contains hundreds of peptides (small proteins) known as conotoxins. (eurekalert.org)
  • A series of newly discovered ω-conotoxins from Conus catus, including CVID-F, are potent and selective antagonists of N-type VGCCs. (edu.au)
  • Neuronally selective μ-conotoxins from Conus striatus utilize an α-hel" by Christina I. Schroeder, Jenny Ekberg et al. (edu.au)
  • Here we report the isolation of μ-conotoxins SIIIA and SIIIB by 125I-TIIIA-guided fractionation of milked Conus striatus venom. (edu.au)
  • α-Conotoxins (α-CgTxs) are a family of Cys-enriched peptides found in several marine snails from the genus Conus. (okstate.edu)
  • Various α-conotoxins isolated from the venoms of Conus snail species provide subtype-selective nAChR antagonists and represent important research tools (although their exquisite specificity can result in differences in recognition of homologous nAChR from different species). (sigmaaldrich.com)
  • Conotoxins are parts of the neurotoxic peptides isolated from the venom of the marine cone snail of the Genus Conus. (biomedcentral.com)
  • The venom of a particular species of cone snail, Conus regius, collected by the Marí group at the Florida Keys, is particularly rich in alpha conotoxins. (eurekalert.org)
  • Many small molecules interact with nAChRs including d-tubocurarine, snake venom protein α-bungarotoxin (α-Bgt), and α-conotoxins, neurotoxic peptides from Conus snails. (tcdb.org)
  • Lebbe EKM, Peigneur S, Wijesekara I, Tytgat J. Conotoxins Targeting Nicotinic Acetylcholine Receptors: An Overview. (mdpi.com)
  • These conotoxins have proven to be valuable pharmacological probes and potential drugs due to their high specificity and affinity to ion channels, receptors, and transporters in the nervous systems of target prey and humans. (mdpi.com)
  • Another family of conotoxins, the α-conotoxins, are competitive antagonists of mammalian nicotinic acetylcholine receptors (nAChRs). (edu.au)
  • Alpha-conotoxins block neuromuscular and neuronal subtypes of nicotinic acetylcholine receptors. (spineuniverse.com)
  • Conotoxins are also active on human receptors (e.g., ion channels), which is of particular interest as they thus can be used as tools to study pain pathways in humans. (eurekalert.org)
  • Addiction is less of a concern, Craik said, because conotoxins act on different receptors in the brain than morphine and other opiate drugs. (eurekalert.org)
  • A subset of these peptides known as α-conotoxins, are antagonists of nicotinic acetylcholine receptors (nAChRs). (frontiersin.org)
  • According to its different targets acting on the organism, the conotoxins can be divided into three categories [3]: (1) acting on voltage-gated ion channels, (2) acting on the ligand-gated ion channel , and (3) acting on other receptors. (thefreedictionary.com)
  • Alpha-conotoxins act on postsynaptic membranes, they bind to the nicotinic acetylcholine receptors (nAChR) and thus inhibit them. (rcsb.org)
  • One class of venom components is the alpha-conotoxins, named so because they target nicotinic receptors that are central to a range of diseases such as Alzheimer's disease, schizophrenia, tobacco addiction and lung cancer. (eurekalert.org)
  • These venomous snails capture prey using a diverse array of unique bioactive neurotoxins, usually named as conotoxins or conopeptides. (mdpi.com)
  • Prof. Dr. Diana Imhof from the Pharmaceutical Institute of the University of Bonn, who is the project's PI, explained, "We are interested in the cone snail's neurotoxins, called conotoxins. (uni-bonn.de)
  • Professor Christie's team also discovered conotoxins appeared to reduce the inflammation at the sites of nerve injuries, as well as possibly having a curative effect. (abc.net.au)
  • Mu-conotoxins block voltage-gated sodium channels (Nav). (rcsb.org)
  • Analgesic conotoxins: block and G protein-coupled receptor modulation " by David J. Adams, Brid P. Callaghan et al. (edu.au)
  • But in humans, Craik says some of these conotoxins appear to have analgesic effects. (eurekalert.org)
  • Conotoxins (conopeptides) are small disulfide bonded peptides from the venom of marine cone snails. (edu.au)
  • Establishing the native disulfide connectivities thus presents a significant challenge when the venom-derived peptide is not available, as is increasingly the case when conotoxins are identified from cDNA sequences. (monash.edu)
  • Conotoxins are bioactive peptides found in the venom that marine cone snails produce for prey capture and defense. (eurekalert.org)
  • Background: Conotoxins are neuro-pharmacologically active cysteine rich peptides isolated from the venom complex of marine cone snails. (iisc.ac.in)
  • Conotoxins like synthesized cone snail venom prevent nerve endings from contracting muscles. (beautybridge.com)
  • Finally, the conotoxins all presynaptically inhibited excitatory synaptic neurotransmission into the dorsal horn and displayed recovery that was largely dependent upon the magnitude of inhibition and not the conotoxin type. (ovid.com)
  • Here, we investigate the disulfide connectivity of mu-conotoxin KIIIA, which was predicted originally to have a [C1-C9,C2-C15,C4-C16] disulfide pattern based on homology with closely related mu-conotoxins. (monash.edu)
  • μ-Conotoxins are small peptide inhibitors of muscle and neuronal tetrodotoxin (TTX)-sensitive voltage-gated sodium channels (VGSCs). (edu.au)
  • Delta-conotoxins activate neuronal sodium channels and are highly toxic to non-mammalian animal systems, and thus may prove useful as pesticides. (spineuniverse.com)
  • Mu-conotoxins block the voltage-dependent sodium channels in muscle tissue and may result in future muscle relaxant and antiseizure compounds. (spineuniverse.com)
  • [17] Mu-conotoxins target the muscle-specific voltage-gated sodium channels, [7] and are useful probes for investigating voltage-dependent sodium channels of excitable tissues. (rug.nl)
  • Structurally related ω-conotoxins bind directly to and selectively inhibit neuronal (N)-type voltage-gated calcium channels (VGCCs) of nociceptive primary afferent neurones. (edu.au)
  • Over 2000 nucleotide and 8000 peptide sequences of conotoxins have been published, and the number is still increasing quickly. (mdpi.com)
  • Conotoxins are short, disulfide-rich peptide toxins produced by aquatic snails. (aps.org)
  • I became acquainted with conotoxins in the Spring 2000 when teaching at the University in Florida. (spineuniverse.com)
  • Targeted re-engineering of native α-conotoxins has resulted in excellent tools for nAChR research as well as potential therapeutics. (frontiersin.org)
  • In the preparation of synthetic conotoxins containing multiple disulfide bonds, oxidative folding can produce numerous permutations of disulfide bond connectivities. (monash.edu)
  • These conotoxins display well-defined, protein-like structures, which are stabilised through multiple disulfide bond frameworks. (eurekalert.org)
  • Sequencing and mass profiling highly modified conotoxins using global reduction/alkylation followed by mass spectrometry. (nih.gov)
  • Gao B, Peng C, Yang J, Yi Y, Zhang J, Shi Q. Cone Snails: A Big Store of Conotoxins for Novel Drug Discovery. (mdpi.com)
  • Conotoxins are disulfide-rich peptides, from the venoms of marine cone snails, which are of pharmaceutical interest because they potently interact with a range of ion channels, transporters and other receptor sites implicated in disease states. (edu.au)
  • These petunias would have been genetically modified to produce small, circular peptides very similar to conotoxins , produced in the wild by a family of marine molluscs called cone snails . (rsc.org)
  • This review aims to give an overview of the knowledge we have today on the molecular pharmacology of conotoxins specifically interacting with nAChRs along with the structure-function relationship data. (mdpi.com)
  • In this case, over 40 conotoxins are characterized based on only two LC-ESI-MS experiments in terms of mass, number of disulfide-linked cysteine residues (and hence, potential toxin superfamilies), relative hydrophobicity, and other posttranslational modifications. (nih.gov)
  • [7] The disulfide bonding network, as well as specific amino acids in inter-cysteine loops, provide the specificity of conotoxins. (rug.nl)
  • Mu-conotoxins have two types of cysteine arrangements, but the knottin scaffold is not observed. (rug.nl)
  • Results: The unusual cysteine arrangements observed suggests novel class of conotoxins. (iisc.ac.in)
  • These results expand our understanding of the diversity of odd cysteine arrangements in conotoxins. (iisc.ac.in)
  • Conotoxins are hypervariable even within the same species. (rug.nl)
  • Each species has its own distinct set of around 100 conotoxins , which like a gourmet chef it mixes in constantly changing proportions, thereby preventing evolution of resistance in their prey. (innovations-report.com)
  • ω-conotoxins, such MVIIA and CVID are effective in neuropathic pain models. (ovid.com)
  • For example, ω-MVIIA was approved by the U.S. Food and Drug Administration in 2004 to treat chronic pain, and nine more conotoxins are at various stages of preclinical or clinical evaluation. (mdpi.com)
  • conotoxins MVIIA and MVIIC on glutamate uptake and on capsaici. (biomedsearch.com)
  • The μ conotoxins contain six cysteines and exist in a folding spectrum. (aps.org)
  • Surprisingly, however, α-conotoxins Vc1.1, RgIA and PeIA more potently inhibit N-type VGCC currents via a GABA B GPCR mechanism in rat sensory neurones. (edu.au)
  • Venomous sea snails use conotoxins to immobilise and kill their prey. (abc.net.au)
  • Cone Snail Glutaminyl Cyclase Sequences from Transcriptomic Analysis and Mass Spectrometric Characterization of Two Pyroglutamyl Conotoxins. (ncbs.res.in)
  • Omega, delta and kappa families of conotoxins have a knottin or inhibitor cystine knot scaffold. (rug.nl)
  • Conotoxins can furthermore be functionalised and provide outstanding leads for new molecular probes: In another paper published in the "Australian Journal of Chemistry", the researchers developed a new methodology to label conotoxins and use them to visualise ion channels in cells. (eurekalert.org)
  • Most conotoxins are a succinct ten to forty amino acids in length and are exquisitely selective about their receptor binding sites. (innovations-report.com)
  • Conotoxins have revolutionised pain research since their extraordinary potency and selectivity enables us to study the individual subtypes of ion channels, which was not possible before," explains Markus Muttenthaler. (eurekalert.org)
  • Among many discoveries, conotoxins that block key neurological pathways have been effective in the early detection and may also help treat small-cell lung cancer, one of the most devastating human cancers. (innovations-report.com)
  • Current research focuses now on conotoxins that could already target nerve endings outside the spinal cord, which would facilitate administration. (eurekalert.org)
  • Experiments suggest that conotoxins could treat muscle spasticity following spinal cord injury. (innovations-report.com)
  • Macdonald Christie, a professor of pharmacology at the University of Sydney, has been looking into the use of conotoxins as part of a study funded by the National Health and Medical Research Council. (abc.net.au)
  • He pointed out that conotoxins are comprised of a spectrum of neuropeptides active on conducting both nerve and muscle tissue. (spineuniverse.com)
  • With the help of conotoxins, researchers can now define the physiological as well as pathological relevance of the different receptor subtypes. (eurekalert.org)
  • Gallo, A. µ-Conotoxins Modulating Sodium Currents in Pain Perception and Transmission: A Therapeutic Potential. (preprints.org)
  • The naturally occurring ù-conotoxins have activity at various Ca channels including the N- (Cav2.2), P/Q- (Cav2.1), R- (Cav2.3), and T- (Cav3.1/3.2) type channels and have served as platforms for the development of therapeutic agents now in development. (pharmiweb.com)
  • Kappa-conotoxins target the voltage-sensitive K ion channel and under investigation as a class of future cardiovascular and gastrointestinal agents. (spineuniverse.com)
  • The number of conotoxins whose activities have been determined so far is five, and they are called the α(alpha)-, δ(delta)-, κ(kappa)-, μ(mu)-, and ω(omega)- types. (rug.nl)
  • Aldo Franco, Ph.D., who worked in Marí's lab, described more than ten new alpha-conotoxins in his Ph.D. dissertation at FAU. (eurekalert.org)