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| Names | |
|---|---|
| IUPAC name cyclo[N-oxa-D-alanyl-D-valyl-N-oxa-L-valyl-D-valyl-N-oxa-D-alanyl-D-valyl-N-oxa-L-valyl-L-valyl-N-oxa-L-alanyl-L-valyl-N-oxa-L-valyl-L-valyl] | |
| Identifiers | |
3D model (JSmol) | |
| ChEBI | |
| ChEMBL | |
| ChemSpider |
|
| DrugBank | |
| ECHA InfoCard | 100.016.270 |
| EC Number |
|
| UNII | |
| UN number | 2811 2588 |
| |
| Properties | |
| C54H90N6O18 | |
| Molar mass | 1111.32 g/mol |
| Appearance | White solid |
| Melting point | 190 °C (374 °F; 463 K) |
| Solubility | Methanol, ethanol, ethyl acetate, petrol-ether, dichloromethane |
| UV-vis (λmax) | 220 nm |
| Hazards | |
| Occupational safety and health (OHS/OSH): | |
Main hazards | Neurotoxicant |
| GHS labelling: | |
 | |
| Danger | |
| H300,H310 | |
| P262,P264,P270,P280,P301+P310,P302+P350,P310,P321,P322,P330,P361,P363,P405,P501 | |
| Lethal dose or concentration (LD, LC): | |
LD50 (median dose) | 4 mg/kg (oral, rat)[1] |
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |
Valinomycin is a naturally occurring dodecadepsipeptide used in the transport ofpotassium and as anantibiotic. Valinomycin is obtained from the cells of severalStreptomyces species,S. fulvissimus being a notable one.
It is a member of the group of natural neutralionophores because it does not have a residual charge. It consists ofenantiomers D- and L-valine (Val), D-alpha-hydroxyisovaleric acid, and L-lactic acid. Structures are alternately bound viaamide andester bridges. Valinomycin is highly selective forpotassium ions oversodium ions within thecell membrane.[2] It functions as a potassium-specific transporter and facilitates the movement of potassium ions through lipid membranes "down" the electrochemical potential gradient.[3] Thestability constant K for the potassium-valinomycin complex is nearly 100,000 times larger than that of the sodium-valinomycin complex.[4]This difference is important for maintaining the selectivity of valinomycin for the transport of potassium ions (and not sodium ions) in biological systems.
It is classified as anextremely hazardous substance in the United States as defined in Section 302 of the U.S.Emergency Planning and Community Right-to-Know Act (42 U.S.C. 11002), and is subject to strict reporting requirements by facilities which produce, store, or use it in significant quantities.[5]
Valinomycin is a dodecadepsipeptide, that is, it is made of twelve alternatingamino acids andesters to form a macrocyclic molecule. The twelvecarbonyl groups are essential for the binding of metal ions, and also forsolvation inpolar solvents. Theisopropyl andmethyl groups are responsible for solvation innonpolar solvents.[6] Along with its shape and size this molecular duality is the main reason for its binding properties. K ions must give up their water of hydration to pass through the pore. K+ ions are octahedrally coordinated in a square bipyramidal geometry by 6 carbonyl bonds from Val. In this space of 1.33 Angstrom, Na+ with its 0.95 Angstrom radius, is significantly smaller than the channel, meaning that Na+ cannot form ionic bonds with the amino acids of the pore at equivalent energy as those it gives up with the water molecules. This leads to a 10,000x selectivity for K+ ions over Na+. For polar solvents, valinomycin will mainly expose the carbonyls to the solvent and in nonpolar solvents the isopropyl groups are located predominantly on the exterior of the molecule. This conformation changes when valinomycin is bound to a potassium ion. The molecule is "locked" into a conformation with the isopropyl groups on the exterior [Citation Needed]. It is not actually locked into configuration because the size of the molecule makes it highly flexible, but the potassium ion gives some degree of coordination to the macromolecule.
Valinomycin was recently reported to be the most potent agent against severe acute respiratory-syndrome coronavirus (SARS-CoV) in infectedVero E6 cells.[7] Valinomycin has been shown to inhibit completelyvaccinia virus in cell based assay in human cell line.[8]
Valinomycin acts as a nonmetallic isoforming agent inpotassium selective electrodes.[9][10]
This ionophore is used to studymembrane vesicles, where it may be selectively applied by experimental design to reduce or eliminate the electrochemical gradient across a membrane.[citation needed]
