Blebbistatin
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Blebbistatin
Blebbistatin is a myosin inhibitor mostly specific for myosin II. It is widely used in research to inhibit heart muscle myosin, non-muscle myosin II, and skeletal muscle myosin. Blebbistatin has been especially useful in optical mapping of the heart, and its recent use in cardiac muscle cell cultures has improved cell survival time. However, its adverse characteristics e.g. its cytotoxicity and blue-light instability or low solubility in water often make its application challenging. Recently its applicability was improved by chemical design and its derivatives overcome the limitations of blebbistatin. E.g. para-nitroblebbistatin and para-aminoblebbistatin are photostable, and they are neither cytotoxic nor fluorescent. Mode of action and biological effects Blebbistatin inhibits myosin ATPase activity and this way acto-myosin based motility. It binds halfway between the nucleotide binding pocket and the actin binding cleft of myosin, predominantly in an actin detached conformati ...
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Para-Aminoblebbistatin
''para''-Aminoblebbistatin is a water-soluble, non-fluorescent, photostable myosin II inhibitor, developed from blebbistatin. Among the several blebbistatin derivatives it is one of the most promising for research applications. Furthermore, it has a favourable overall profile considering inhibitory properties and ADME ADME is an abbreviation in pharmacokinetics and pharmacology for "absorption, distribution, metabolism, and excretion", and describes the disposition of a pharmaceutical compound within an organism. The four criteria all influence the drug level ... calculations. Myosin specificity References {{DEFAULTSORT:Aminoblebbistatin, para- Anilines Pyrroloquinolines Acyloins Tertiary alcohols ...
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Para-aminoblebbistatin 2D Structure
''para''-Aminoblebbistatin is a water-soluble, non-fluorescent, photostable myosin II inhibitor, developed from blebbistatin. Among the several blebbistatin derivatives it is one of the most promising for research applications. Furthermore, it has a favourable overall profile considering inhibitory properties and ADME ADME is an abbreviation in pharmacokinetics and pharmacology for "absorption, distribution, metabolism, and excretion", and describes the disposition of a pharmaceutical compound within an organism. The four criteria all influence the drug level ... calculations. Myosin specificity References {{DEFAULTSORT:Aminoblebbistatin, para- Anilines Pyrroloquinolines Acyloins Tertiary alcohols ...
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Bleb (cell Biology)
In cell biology, a bleb is a bulge of the plasma membrane of a cell, characterized by a spherical, bulky morphology. It is characterized by the decoupling of the cytoskeleton from the plasma membrane, degrading the internal structure of the cell, allowing the flexibility required for the cell to separate into individual bulges or pockets of the intercellular matrix. Most commonly, blebs are seen in apoptosis (programmed cell death) but are also seen in other non-apoptotic functions. ''Blebbing'', or ''zeiosis'', is the formation of blebs. Formation Initiation and expansion Bleb growth is driven by intracellular pressure generated in the cytoplasm when the actin cortex undergoes actomyosin contractions. The disruption of the membrane-actin cortex interactions are dependent on the activity of myosin-ATPase Bleb initiation is affected by three main factors: high intracellular pressure, decreased amounts of cortex-membrane linker proteins, and deterioration of the actin cortex ...
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Myosin
Myosins () are a superfamily of motor proteins best known for their roles in muscle contraction and in a wide range of other motility processes in eukaryotes. They are ATP-dependent and responsible for actin-based motility. The first myosin (M2) to be discovered was in 1864 by Wilhelm Kühne. Kühne had extracted a viscous protein from skeletal muscle that he held responsible for keeping the tension state in muscle. He called this protein ''myosin''. The term has been extended to include a group of similar ATPases found in the cells of both striated muscle tissue and smooth muscle tissue. Following the discovery in 1973 of enzymes with myosin-like function in ''Acanthamoeba castellanii'', a global range of divergent myosin genes have been discovered throughout the realm of eukaryotes. Although myosin was originally thought to be restricted to muscle cells (hence '' myo-''(s) + '' -in''), there is no single "myosin"; rather it is a very large superfamily of genes whose prote ...
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Scallop
Scallop () is a common name that encompasses various species of marine bivalve mollusks in the taxonomic family Pectinidae, the scallops. However, the common name "scallop" is also sometimes applied to species in other closely related families within the superfamily Pectinoidea, which also includes the thorny oysters. Scallops are a cosmopolitan family of bivalves found in all of the world's oceans, although never in fresh water. They are one of the very few groups of bivalves to be primarily "free-living", with many species capable of rapidly swimming short distances and even migrating some distance across the ocean floor. A small minority of scallop species live cemented to rocky substrates as adults, while others attach themselves to stationary or rooted objects such as seagrass at some point in their lives by means of a filament they secrete called a byssal thread. The majority of species, however, live recumbent on sandy substrates, and when they sense the presence of a ...
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Structure–activity Relationship
The structure–activity relationship (SAR) is the relationship between the chemical structure of a molecule and its biological activity. This idea was first presented by Crum-Brown and Fraser in 1865. The analysis of SAR enables the determination of the chemical group responsible for evoking a target biological effect in the organism. This allows modification of the effect or the potency of a bioactive compound (typically a drug) by changing its chemical structure. Medicinal chemists use the techniques of chemical synthesis to insert new chemical groups into the biomedical compound and test the modifications for their biological effects. This method was refined to build mathematical relationships between the chemical structure and the biological activity, known as quantitative structure–activity relationships (QSAR). A related term is structure affinity relationship (SAFIR). Structure-biodegradability relationship The large number of synthetic organic chemicals currently in p ...
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Two-photon Excitation Microscopy
Two-photon excitation microscopy (TPEF or 2PEF) is a fluorescence imaging technique that allows imaging of living tissue up to about one millimeter in thickness, with 0.64 μm lateral and 3.35 μm axial spatial resolution. Unlike traditional fluorescence microscopy, in which the excitation wavelength is shorter than the emission wavelength, two-photon excitation requires simultaneous excitation by two photons with longer wavelength than the emitted light. Two-photon excitation microscopy typically uses near-infrared (NIR) excitation light which can also excite fluorescent dyes. However, for each excitation, two photons of NIR light are absorbed. Using infrared light minimizes scattering in the tissue. Due to the multiphoton absorption, the background signal is strongly suppressed. Both effects lead to an increased penetration depth for this technique. Two-photon excitation can be a superior alternative to confocal microscopy due to its deeper tissue penetration, efficient light ...
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Photoaffinity Labeling
Photoaffinity labeling is a chemoproteomics technique used to attach "labels" to the active site of a large molecule, especially a protein. The "label" attaches to the molecule loosely and reversibly, and has an inactive site which can be converted using photolysis into a highly reactive form, which causes the label to bind more permanently to the large molecule via a covalent bond. The technique was first described in the 1970s. Molecules that have been used as labels in this process are often analogs of complex molecules, in which certain functional groups are replaced with a photoreactive group, such as an azide, a diazirine or a benzophenone Benzophenone is the organic compound with the formula (C6H5)2CO, generally abbreviated Ph2CO. It is a white solid that is soluble in organic solvents. Benzophenone is a widely used building block in organic chemistry, being the parent diarylket .... References {{Reflist Molecular biology techniques ...
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Cnidaria
Cnidaria () is a phylum under kingdom Animalia containing over 11,000 species of aquatic animals found both in freshwater and marine environments, predominantly the latter. Their distinguishing feature is cnidocytes, specialized cells that they use mainly for capturing prey. Their bodies consist of mesoglea, a non-living jelly-like substance, sandwiched between two layers of epithelium that are mostly one cell thick. Cnidarians mostly have two basic body forms: swimming medusae and sessile polyps, both of which are radially symmetrical with mouths surrounded by tentacles that bear cnidocytes. Both forms have a single orifice and body cavity that are used for digestion and respiration. Many cnidarian species produce colonies that are single organisms composed of medusa-like or polyp-like zooids, or both (hence they are trimorphic). Cnidarians' activities are coordinated by a decentralized nerve net and simple receptors. Several free-swimming species of Cubozoa and Scy ...
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