Phalloidin
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Phalloidin
Phalloidin belongs to a class of toxins called phallotoxins, which are found in the death cap mushroom ''(Amanita phalloides)''. It is a rigid bicyclic heptapeptide that is lethal after a few days when injected into the bloodstream. The major symptom of phalloidin poisoning is acute hunger due to the destruction of liver cells. It functions by binding and stabilizing filamentous actin (F-actin) and effectively prevents the depolymerization of actin fibers. Due to its tight and selective binding to F-actin, derivatives of phalloidin containing fluorescent tags are used widely in microscopy to visualize F-actin in biomedical research. Discovery and background Phalloidin was one of the first cyclic peptides to be discovered. It was isolated from the death cap mushroom and crystallized by Feodor Lynen and Ulrich WielandG. Semenza, E.C. Slater, R. JaenickeSelected Topics in the History of Biochemistry. Personal Recollections- Google books in 1937. Its structure is unusual in that it co ...
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Phalloidin Staining Of Actin Filaments
Phalloidin belongs to a class of toxins called phallotoxins, which are found in the death cap mushroom ''(Amanita phalloides)''. It is a rigid bicyclic heptapeptide that is lethal after a few days when injected into the bloodstream. The major symptom of phalloidin poisoning is acute hunger due to the destruction of liver cells. It functions by binding and stabilizing filamentous actin (F-actin) and effectively prevents the depolymerization of actin fibers. Due to its tight and selective binding to F-actin, derivatives of phalloidin containing fluorescent tags are used widely in microscopy to visualize F-actin in biomedical research. Discovery and background Phalloidin was one of the first cyclic peptides to be discovered. It was isolated from the death cap mushroom and crystallized by Feodor Lynen and Ulrich WielandG. Semenza, E.C. Slater, R. JaenickeSelected Topics in the History of Biochemistry. Personal Recollections- Google books in 1937. Its structure is unusual in that it co ...
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Phalloidin Synthetic Scheme
Phalloidin belongs to a class of toxins called phallotoxins, which are found in the death cap mushroom ''(Amanita phalloides)''. It is a rigid bicyclic heptapeptide that is lethal after a few days when injected into the bloodstream. The major symptom of phalloidin poisoning is acute hunger due to the destruction of liver cells. It functions by binding and stabilizing filamentous actin (F-actin) and effectively prevents the depolymerization of actin fibers. Due to its tight and selective binding to F-actin, derivatives of phalloidin containing fluorescent tags are used widely in microscopy to visualize F-actin in biomedical research. Discovery and background Phalloidin was one of the first cyclic peptides to be discovered. It was isolated from the death cap mushroom and crystallized by Feodor Lynen and Ulrich WielandG. Semenza, E.C. Slater, R. JaenickeSelected Topics in the History of Biochemistry. Personal Recollections- Google books in 1937. Its structure is unusual in that it co ...
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Actin Inhibitors
Cytoskeletal drugs are small molecules that interact with actin or tubulin. These drugs can act on the cytoskeletal components within a cell in three main ways. Some cytoskeletal drugs stabilize a component of the cytoskeleton, such as taxol, which stabilizes microtubules, or Phalloidin, which stabilizes actin filaments. Others, such as Cytochalasin D, bind to actin monomers and prevent them from polymerizing into filaments. Drugs such as demecolcine act by enhancing the depolymerisation of already formed microtubules. Some of these drugs have multiple effects on the cytoskeleton: for example, Latrunculin both prevents actin polymerization as well as enhancing its rate of depolymerization. Typically the microtubule targeting drugs can be found in the clinic where they are used therapeutically in the treatment of some forms of cancer. As a result of the lack of specificity for specific type of actin (i.e. cannot distinguish between cardiac, smooth muscle, muscle and cytoskeletal for ...
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Phallotoxins
The phallotoxins consist of at least seven compounds, all of which are bicyclic heptapeptides (seven amino acids), isolated from the death cap mushroom ''(Amanita phalloides)''. They differ from the closely related amatoxins by being one residue smaller, both in the final product and the precursor protein. Phalloidin had been isolated in 1937 by Feodor Lynen, Heinrich Wieland's student and son-in-law, and Ulrich Wieland of the University of Munich. The remaining six are prophalloin, phalloin, phallisin, phallacidin, phallacin and phallisacin. Though highly toxic to liver cells, phallotoxins have since been found to have little contribution to the death cap's toxicity because they are not absorbed through the gut. Reports of phalloidin in the edible (and sought after) Blusher The blusher is the common name for several closely related species of the genus ''Amanita''. ''A. rubescens'' or the blushing amanita, is found in Europe and eastern North America, and ''A. novinupta'' ...
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Actin
Actin is a family of globular multi-functional proteins that form microfilaments in the cytoskeleton, and the thin filaments in muscle fibrils. It is found in essentially all eukaryotic cells, where it may be present at a concentration of over 100 μM; its mass is roughly 42 kDa, with a diameter of 4 to 7 nm. An actin protein is the monomeric subunit of two types of filaments in cells: microfilaments, one of the three major components of the cytoskeleton, and thin filaments, part of the contractile apparatus in muscle cells. It can be present as either a free monomer called G-actin (globular) or as part of a linear polymer microfilament called F-actin (filamentous), both of which are essential for such important cellular functions as the mobility and contraction of cells during cell division. Actin participates in many important cellular processes, including muscle contraction, cell motility, cell division and cytokinesis, vesicle and organelle movement, cell sign ...
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Amanita Phalloides
''Amanita phalloides'' (), commonly known as the death cap, is a deadly poisonous basidiomycete fungus, one of many in the genus ''Amanita''. Widely distributed across Europe, but now sprouting in other parts of the world, ''A. phalloides'' forms ectomycorrhizas with various broadleaved trees. In some cases, the death cap has been introduced to new regions with the cultivation of non-native species of oak, chestnut, and pine. The large fruiting bodies (mushrooms) appear in summer and autumn; the caps are generally greenish in colour with a white stipe and gills. The cap colour is variable, including white forms, and is thus not a reliable identifier. These toxic mushrooms resemble several edible species (most notably Caesar's mushroom and the straw mushroom) commonly consumed by humans, increasing the risk of accidental poisoning. Amatoxins, the class of toxins found in these mushrooms, are thermostable: they resist changes due to heat, so their toxic effects are not red ...
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Mycotoxins Found In Basidiomycota
A mycotoxin (from the Greek μύκης , "fungus" and τοξίνη , "toxin") is a toxic secondary metabolite produced by organisms of kingdom Fungi and is capable of causing disease and death in both humans and other animals. The term 'mycotoxin' is usually reserved for the toxic chemical products produced by fungi that readily colonize crops. Examples of mycotoxins causing human and animal illness include aflatoxin, citrinin, fumonisins, ochratoxin A, patulin, trichothecenes, zearalenone, and ergot alkaloids such as ergotamine. One mold species may produce many different mycotoxins, and several species may produce the same mycotoxin. Production Most fungi are aerobic (use oxygen) and are found almost everywhere in extremely small quantities due to the diminute size of their spores. They consume organic matter wherever humidity and temperature are sufficient. Where conditions are right, fungi proliferate into colonies and mycotoxin levels become high. The reason for the producti ...
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Cytoskeleton
The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is composed of similar proteins in the various organisms. It is composed of three main components, microfilaments, intermediate filaments and microtubules, and these are all capable of rapid growth or disassembly dependent on the cell's requirements. A multitude of functions can be performed by the cytoskeleton. Its primary function is to give the cell its shape and mechanical resistance to deformation, and through association with extracellular connective tissue and other cells it stabilizes entire tissues. The cytoskeleton can also contract, thereby deforming the cell and the cell's environment and allowing cells to migrate. Moreover, it is involved in many cell signaling pathways and in the uptake of extracellular material ( endocytosis), the ...
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Eosin
Eosin is the name of several fluorescent acidic compounds which bind to and form salts with basic, or eosinophilic, compounds like proteins containing amino acid residues such as arginine and lysine, and stains them dark red or pink as a result of the actions of bromine on eosin. In addition to staining proteins in the cytoplasm, it can be used to stain collagen and muscle fibers for examination under the microscope. Structures, that stain readily with eosin, are termed eosinophilic. In the field of histology, Eosin Y is the form of eosin used most often as a histologic stain. Etymology Eosin was named by its inventor Heinrich Caro after the nickname (Eos) of a childhood friend, Anna Peters. Variants There are actually two very closely related compounds commonly referred to as eosin. Most often used is in histology is Eosin Y (also known as eosin Y ws, eosin yellowish, Acid Red 87, C.I. 45380, bromoeosine, bromofluoresceic acid, D&C Red No. 22); it has a very slightly yellowi ...
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Intraperitoneal Injection
Intraperitoneal injection or IP injection is the injection of a substance into the peritoneum (body cavity). It is more often applied to animals than to humans. In general, it is preferred when large amounts of blood replacement fluids are needed or when low blood pressure or other problems prevent the use of a suitable blood vessel for intravenous injection. In humans, the method is widely used to administer chemotherapy drugs to treat some cancers, particularly ovarian cancer. Although controversial, intraperitoneal use in ovarian cancer has been recommended as a standard of care. Fluids are injected intraperitoneally in infants, also used for peritoneal dialysis. Background Intraperitoneal injections are a way to administer therapeutics and drugs through a peritoneal route (body cavity). They are one of the few ways drugs can be administered through injection, and have uses in research involving animals, drug administration to treat ovarian cancers, and much more. Understanding ...
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Median Lethal Dose
In toxicology, the median lethal dose, LD50 (abbreviation for "lethal dose, 50%"), LC50 (lethal concentration, 50%) or LCt50 is a toxic unit that measures the lethal dose of a toxin, radiation, or pathogen. The value of LD50 for a substance is the dose required to kill half the members of a tested population after a specified test duration. LD50 figures are frequently used as a general indicator of a substance's acute toxicity. A lower LD50 is indicative of increased toxicity. The test was created by J.W. Trevan in 1927. The term semilethal dose is occasionally used in the same sense, in particular with translations of foreign language text, but can also refer to a sublethal dose. LD50 is usually determined by tests on animals such as laboratory mice. In 2011, the U.S. Food and Drug Administration approved alternative methods to LD50 for testing the cosmetic drug Botox without animal tests. Conventions The LD50 is usually expressed as the mass of substance administered per unit ...
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