Conantokins
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Conantokins
Conantokins are a small family of helical peptides that are derived from the venom of predatory marine snails of the genus ''Conus''. Conantokins act as potent and specific antagonists of the N-methyl-D-aspartate receptor (NMDAR). They are the only naturally-derived peptides to do so. The subtypes of conantokins exhibit a surprising variability of selectivity across the NMDAR subunits, and are therefore uniquely useful in developing subunit-specific pharmacological probes. Chemically, conantokins are unique in that they possess a number (generally 4 or 5) of gamma-carboxyglutamyl (Gla) residues, generated by the post-translational modification of glutamyl (Glu) residues. These Gla residues induce a conformational change from a 3 10 helix to an alpha helix on binding to Calcium. In the broader scheme of genetic conotoxin classification, Conanotokins are also known as "Conotoxin Superfamily B." The word "conantokin" is derived from the Filipino word ''antokin'', meaning sleepy. S ...
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Conotoxin
A conotoxin is one of a group of neurotoxic peptides isolated from the venom of the marine cone snail, genus ''Conus''. Conotoxins, which are peptides consisting of 10 to 30 amino acid residues, typically have one or more disulfide bonds. Conotoxins have a variety of mechanisms of actions, most of which have not been determined. However, it appears that many of these peptides modulate the activity of ion channels. Over the last few decades conotoxins have been the subject of pharmacological interest. The LD50 of conotoxin ranges from 5-25 μg/kg. Hypervariability Conotoxins are hypervariable even within the same species. They do not act within a body where they are produced (endogenously) but act on other organisms. Therefore, conotoxin genes experience less selection against mutations (like gene duplication and nonsynonymous substitution), and mutations remain in the genome longer, allowing more time for potentially beneficial novel functions to arise. Variability in c ...
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Peptides
Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A polypeptide is a longer, continuous, unbranched peptide chain. Hence, peptides fall under the broad chemical classes of biological polymers and oligomers, alongside nucleic acids, oligosaccharides, polysaccharides, and others. A polypeptide that contains more than approximately 50 amino acids is known as a protein. Proteins consist of one or more polypeptides arranged in a biologically functional way, often bound to ligands such as coenzymes and cofactors, or to another protein or other macromolecule such as DNA or RNA, or to complex macromolecular assemblies. Amino acids that have been incorporated into peptides are termed residues. A water molecule is released during formation of each amide bond.. All peptides except cyclic peptides ...
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Drug Addiction
Addiction is a neuropsychological disorder characterized by a persistent and intense urge to engage in certain behaviors, one of which is the usage of a drug, despite substantial harm and other negative consequences. Repetitive drug use often alters brain function in ways that perpetuate craving, and weakens (but does not completely negate) self-control. This phenomenon – drugs reshaping brain function – has led to an understanding of addiction as a brain disorder with a complex variety of psychosocial as well as neurobiological (and thus involuntary) factors that are implicated in addiction's development. Classic signs of addiction include compulsive engagement in rewarding stimuli, ''preoccupation'' with substances or behavior, and continued use despite negative consequences. Habits and patterns associated with addiction are typically characterized by immediate gratification (short-term reward), coupled with delayed deleterious effects (long-term costs). Examples o ...
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GRIN2C
Glutamate MDAreceptor subunit epsilon-3 is a protein that in humans is encoded by the ''GRIN2C'' gene. Function N-methyl-D-aspartate (NMDA) receptors are a class of ionotropic glutamate receptors. NMDA channel has been shown to be involved in long-term potentiation, an activity-dependent increase in the efficiency of synaptic transmission thought to underlie certain kinds of memory and learning. NMDA receptor channels are heteromers composed of the key receptor subunit NMDAR1 (GRIN1) and 1 or more of the 4 NMDAR2 subunits: NMDAR2A ( GRIN2A), NMDAR2B (GRIN2B), NMDAR2C (GRIN2C), and NMDAR2D ( GRIN2D). Interactions GRIN2C has been shown to interact with DLG4 and DLG3. See also * Glutamate receptor * NMDA receptor The ''N''-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and ion channel found in neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the other two being AMPA rece ... Referenc ...
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Disulfide
In biochemistry, a disulfide (or disulphide in British English) refers to a functional group with the structure . The linkage is also called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups. In biology, disulfide bridges formed between thiol groups in two cysteine residues are an important component of the secondary and tertiary structure of proteins. ''Persulfide'' usually refers to compounds. In inorganic chemistry disulfide usually refers to the corresponding anion (−S−S−). Organic disulfides Symmetrical disulfides are compounds of the formula . Most disulfides encountered in organo sulfur chemistry are symmetrical disulfides. Unsymmetrical disulfides (also called heterodisulfides) are compounds of the formula . They are less common in organic chemistry, but most disulfides in nature are unsymmetrical. Properties The disulfide bonds are strong, with a typical bond dissociation energy of 60 kcal/mol (251&nbs ...
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Conus Ermineus
''Conus ermineus'', common name the turtle cone, is a species of sea snail, a marine gastropod mollusk in the family Conidae, the cone snails and their allies. Like all species within the genus ''Conus'', these snails are predatory and venomous. They are capable of "stinging" humans, therefore live ones should be handled carefully or not at all. Distribution This species occurs in the Caribbean Sea and the Gulf of Mexico to South America; in the Atlantic Ocean off West Africa and the Cape Verdes; in the Indian Ocean off Tanzania. Description The maximum recorded shell Shell may refer to: Architecture and design * Shell (structure), a thin structure ** Concrete shell, a thin shell of concrete, usually with no interior columns or exterior buttresses ** Thin-shell structure Science Biology * Seashell, a hard o ... length is 103 mm.Welch J. J. (2010). "The "Island Rule" and Deep-Sea Gastropods: Re-Examining the Evidence". '' PLoS ONE'' 5(1): e8776. . Conantokin-E ...
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Conus Purpurascens
''Conus purpurascens'', common name the purple cone, is a species of sea snail, a marine gastropod mollusk in the family Conidae, the cone snails and their allies. Like all species within the genus ''Conus'', these snails are predatory and venomous. They are capable of "stinging" humans, therefore live ones should be handled carefully or not at all. Conantokin-P is a toxin derived from the venom of ''Conus purpurascens''. Description The size of the shell varies between 33 mm and 80 mm. The shell is broad-shouldered, with a rude, striate spire. It is striate below, and the string sometimes is slightly granular. The shell is clouded with white or violaceous and brown or olive, with close lines of chestnut and white minute articulations. Sometimes it is irregularly white-banded in the middle. The color variations of this handsome species are dazzling, but the general habit of the shell is quite constant. (Original description of ''Conus purpurascens'' var. ''rejectus'' ...
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GRIN2B
Glutamate MDAreceptor subunit epsilon-2, also known as ''N''-methyl D-aspartate receptor subtype 2B (NMDAR2B or NR2B), is a protein that in humans is encoded by the ''GRIN2B'' gene. NMDA receptors ''N''-methyl-D-aspartate (NMDA) receptors are a class of ionotropic glutamate receptors. The NMDA receptor channel has been shown to be involved in long-term potentiation, an activity-dependent increase in the efficiency of synaptic transmission thought to underlie certain kinds of memory and learning. NMDA receptor channels are heterotetramers composed of two molecules of the key receptor subunit NMDAR1 (GRIN1) and two drawn from one or more of the four NMDAR2 subunits: NMDAR2A ( GRIN2A), NMDAR2B (GRIN2B), NMDAR2C ( GRIN2C), and NMDAR2D ( GRIN2D). The NR2 subunit acts as the agonist binding site for glutamate, one of the predominant excitatory neurotransmitter receptors in the mammalian brain. Function NR2B has been associated with age- and visual-experience-dependent plasticity in ...
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Conus Parius
''Conus parius'', common name the Parian cone, is a species of sea snail, a marine gastropod mollusk in the family Conidae, the cone snails and their allies. Like all species within the genus ''Conus'', these snails are predatory and venomous. They are capable of "stinging" humans, therefore live ones should be handled carefully or not at all. Description The size of the shell varies between 25 mm and 46 mm. The color of the shell is white to pale yellowish, often longitudinally indistinctly marked with deeper coloring. The spire is striate. The lower part of the body whorl is distantly sulcate. Conantokin-Pr1, -Pr2 and -Pr3 are toxins derived from the venom of Conus parius. These small neurotoxic peptides have been found to act as NMDA antagonists ''in vitro'', and stimulate production of the transcription factor CREB in the brain. Distribution This marine species occurs off the Philippines and Indonesia; off Papua New Guinea, the Solomon Islands and Vanuatu Va ...
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Conus Lynceus
''Conus lynceus'' , the lynceus cone, is a species of predatory sea snail, a marine gastropod mollusk in the family Conidae, the cone snails, cone shells or cones. Like all species within the genus Conus, these snails are predatory and venomous. They are capable of "stinging" humans, therefore live ones should be handled carefully or not at all. Description Conantokin-L is a toxin derived from the venom of Conus lynceus. Distribution This is an Indo-Pacific species found along Taiwan, the Philippines, Java, Solomon Islands, Queensland, Australia. Shell description The size of an adult shell varies between 50 mm and 89 mm. The shell is somewhat swollen, distantly sulcate below, otherwise smooth. The shell is white with encircled by chestnut spots, clouds, and oblique and triangular markings. It has a very pointed, maculated spire.George Washington Tryon, Manual of Conchology vol. VI, p. 56; 1879 (described as ''Conus nisus'' Chemn.) References * Hinton, A. 197 ...
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Conus Radiatus
''Conus radiatus'', common name the rayed cone, is a species of sea snail, a marine gastropod mollusk in the family Conidae, the cone snails and their allies. Like all species within the genus ''Conus'', these snails are predatory and venomous. They are capable of "stinging" humans, therefore live ones should be handled carefully or not at all. Description The size of the shell varies between 30 mm and 109 mm. The color of the shell is pale yellowish to pale chestnut, often longitudinally indistinctly marked with deeper coloring. The spire is striate. The lower part of body whorl is distantly sulcate. The white variety is frequently covered by a smooth olivaceous epidermis. Conantokin-C is a toxin derived from the venom of ''Conus radiatus''. Distribution This marine species occurs off the Philippines, New Guinea and Fiji Fiji ( , ,; fj, Viti, ; Fiji Hindi: फ़िजी, ''Fijī''), officially the Republic of Fiji, is an island country in Melanesia, pa ...
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Anticonvulsant
Anticonvulsants (also known as antiepileptic drugs or recently as antiseizure drugs) are a diverse group of pharmacological agents used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder and borderline personality disorder, since many seem to act as mood stabilizers, and for the treatment of neuropathic pain. Anticonvulsants suppress the excessive rapid firing of neurons during seizures. Anticonvulsants also prevent the spread of the seizure within the brain. Conventional antiepileptic drugs may block sodium channels or enhance γ-aminobutyric acid ( GABA) function. Several antiepileptic drugs have multiple or uncertain mechanisms of action. Next to the voltage-gated sodium channels and components of the GABA system, their targets include GABAA receptors, the GAT-1 GABA transporter, and GABA transaminase. Additional targets include voltage-gated calcium channels, SV2A, and α2δ. By blocking sodium or ca ...
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