A23187
Encyclopedia
A23187 is a mobile ion-carrier that forms stable complexes with divalent cations (ion
s with a charge of +2). A23187 is also known as Calcimycin, Calcium Ionophore
, Antibiotic A23187 and Calcium Ionophore
A23187. It is produced at fermentation
of Streptomyces
Chartreusensis.
properties against gram positive bacteria
and fungi
. It also acts as a divalent cation ionophore
, allowing these ions to cross cell membrane
s, which are usually impermeable to them. A23187 is most selective for Mn2+, somewhat less selective for Ca2+
and Mg2+
, much less selective for Sr2+
, and even less selective for Ba2+
. The ionophore is used in laboratories to increase intracellular Ca2+ levels in intact cell
s. It also uncouples oxidative phosphorylation
, the process cells use to synthesize Adenosine triphosphate
which they use for energy. In addition, A23187 inhibits mitochondrial ATPase
activity. A23187 also induces apoptosis in some cells (e.g. mouse lymphoma
cell line, or S49, and Jurkat cells
) and prevents it in others (e.g. cells dependent on interleukin 3
that have had the factor withdrawn).
Inex Pharmaceuticals Corporation (Canada) reported an innovative application of A23187. Inex used A23187 as a molecular tool in order to make artificial liposomes loaded with anti-cancer
drugs such as Topotecan
.
, Ca2+ salt, and 4-brominated analog.
Ion
An ion is an atom or molecule in which the total number of electrons is not equal to the total number of protons, giving it a net positive or negative electrical charge. The name was given by physicist Michael Faraday for the substances that allow a current to pass between electrodes in a...
s with a charge of +2). A23187 is also known as Calcimycin, Calcium Ionophore
Ionophore
An ionophore is a lipid-soluble molecule usually synthesized by microorganisms to transport ions across the lipid bilayer of the cell membrane...
, Antibiotic A23187 and Calcium Ionophore
Ionophore
An ionophore is a lipid-soluble molecule usually synthesized by microorganisms to transport ions across the lipid bilayer of the cell membrane...
A23187. It is produced at fermentation
Fermentation (biochemistry)
Fermentation is the process of extracting energy from the oxidation of organic compounds, such as carbohydrates, using an endogenous electron acceptor, which is usually an organic compound. In contrast, respiration is where electrons are donated to an exogenous electron acceptor, such as oxygen,...
of Streptomyces
Streptomyces
Streptomyces is the largest genus of Actinobacteria and the type genus of the family Streptomycetaceae. Over 500 species of Streptomyces bacteria have been described. As with the other Actinobacteria, streptomycetes are gram-positive, and have genomes with high guanine and cytosine content...
Chartreusensis.
Actions and uses
A23187 has antibioticAntibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
properties against gram positive bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
and fungi
Fungus
A fungus is a member of a large group of eukaryotic organisms that includes microorganisms such as yeasts and molds , as well as the more familiar mushrooms. These organisms are classified as a kingdom, Fungi, which is separate from plants, animals, and bacteria...
. It also acts as a divalent cation ionophore
Ionophore
An ionophore is a lipid-soluble molecule usually synthesized by microorganisms to transport ions across the lipid bilayer of the cell membrane...
, allowing these ions to cross cell membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
s, which are usually impermeable to them. A23187 is most selective for Mn2+, somewhat less selective for Ca2+
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
and Mg2+
Magnesium
Magnesium is a chemical element with the symbol Mg, atomic number 12, and common oxidation number +2. It is an alkaline earth metal and the eighth most abundant element in the Earth's crust and ninth in the known universe as a whole...
, much less selective for Sr2+
Strontium
Strontium is a chemical element with the symbol Sr and the atomic number 38. An alkaline earth metal, strontium is a soft silver-white or yellowish metallic element that is highly reactive chemically. The metal turns yellow when exposed to air. It occurs naturally in the minerals celestine and...
, and even less selective for Ba2+
Barium
Barium is a chemical element with the symbol Ba and atomic number 56. It is the fifth element in Group 2, a soft silvery metallic alkaline earth metal. Barium is never found in nature in its pure form due to its reactivity with air. Its oxide is historically known as baryta but it reacts with...
. The ionophore is used in laboratories to increase intracellular Ca2+ levels in intact cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
s. It also uncouples oxidative phosphorylation
Oxidative phosphorylation
Oxidative phosphorylation is a metabolic pathway that uses energy released by the oxidation of nutrients to produce adenosine triphosphate . Although the many forms of life on earth use a range of different nutrients, almost all aerobic organisms carry out oxidative phosphorylation to produce ATP,...
, the process cells use to synthesize Adenosine triphosphate
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
which they use for energy. In addition, A23187 inhibits mitochondrial ATPase
ATPase
ATPases are a class of enzymes that catalyze the decomposition of adenosine triphosphate into adenosine diphosphate and a free phosphate ion. This dephosphorylation reaction releases energy, which the enzyme harnesses to drive other chemical reactions that would not otherwise occur...
activity. A23187 also induces apoptosis in some cells (e.g. mouse lymphoma
Lymphoma
Lymphoma is a cancer in the lymphatic cells of the immune system. Typically, lymphomas present as a solid tumor of lymphoid cells. Treatment might involve chemotherapy and in some cases radiotherapy and/or bone marrow transplantation, and can be curable depending on the histology, type, and stage...
cell line, or S49, and Jurkat cells
Jurkat cells
Jurkat cells are an immortalized line of T lymphocyte cells that are used to study acute T cell leukemia, T cell signaling, and the expression of various chemokine receptors susceptible to viral entry, particularly HIV. Jurkat cells are also useful in science because of their ability to produce...
) and prevents it in others (e.g. cells dependent on interleukin 3
Interleukin 3
Interleukin 3, also known as IL-3, is a protein that in humans is encoded by the IL3 gene.-Function:Interleukin-3 is an interleukin, a type of biological signal that can improve the body's natural response to disease as part of the immune system...
that have had the factor withdrawn).
Inex Pharmaceuticals Corporation (Canada) reported an innovative application of A23187. Inex used A23187 as a molecular tool in order to make artificial liposomes loaded with anti-cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
drugs such as Topotecan
Topotecan
Topotecan hydrochloride is a chemotherapy agent that is a topoisomerase I inhibitor. It is the water-soluble derivative of camptothecin...
.
Biosynthesis
The core siosynthetic enzymes are thought to include 3 proteins for the biosynthesis of the α-ketopyrrole moiety, 5 for modular type I polyketide synthases for the spiroketal ring, 4 for the biosynthesis of 3-hydroxyanthranilic acid, an N-methyltransferase tailoring enzyme, and a type II thioesterase.Commercial availability
Commercially, A23187 is available as free acidAcid
An acid is a substance which reacts with a base. Commonly, acids can be identified as tasting sour, reacting with metals such as calcium, and bases like sodium carbonate. Aqueous acids have a pH of less than 7, where an acid of lower pH is typically stronger, and turn blue litmus paper red...
, Ca2+ salt, and 4-brominated analog.