valinomycin

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| Watchedfields = changed

| verifiedrevid = 470628010

| ImageFile = Valinomycin.svg

| ImageSize =

| ImageAlt = Skeletal formula of valinomycin

| ImageFile1 = Valinomycin 3D ball.png

| ImageAlt1 = Ball-and-stick model of the valinomycin molecule

| IUPACName = 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]

| OtherNames =

|Section1={{Chembox Identifiers

| Abbreviations =

| ChEBI_Ref = {{ebicite|correct|EBI}}

| ChEBI = 28545

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 21493802

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 223643

| CASNo_Ref = {{cascite|correct|CAS}}

| CASNo = 2001-95-8

| DrugBank = DB14057

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = N561YS75MN

| UNNumber = 2811 2588

| EINECS = 217-896-6

| PubChem = 3000706

| SMILES = C[C@@H]1C(=O)N[C@@H](C(=O)O[C@H](C(=O)N[C@@H](C(=O)O[C@@H](C(=O)N[C@@H](C(=O)O[C@H](C(=O)N[C@H](C(=O)O[C@H](C(=O)N[C@H](C(=O)O[C@H](C(=O)N[C@H](C(=O)O1)C(C)C)C(C)C)C(C)C)C)C(C)C)C(C)C)C(C)C)C)C(C)C)C(C)C)C(C)C

| SMILES_Comment = {{Cite web | url=https://chem.nlm.nih.gov/chemidplus/rn/2001-95-8 | title=ChemIDplus - 2001-95-8 - FCFNRCROJUBPLU-DNDCDFAISA-N - Valinomycin - Similar structures search, synonyms, formulas, resource links, and other chemical information | url-status = dead | archive-url = https://web.archive.org/web/20151220095207/https://chem.nlm.nih.gov/chemidplus/rn/2001-95-8 | archive-date = 20 December 2015 | website = TOXNET | publisher = U.S. National Library of Medicine}}

| InChI = 1S/C54H90N6O18/c1-22(2)34-49(67)73-31(19)43(61)55-38(26(9)10)53(71)77-41(29(15)16)47(65)59-36(24(5)6)51(69)75-33(21)45(63)57-39(27(11)12)54(72)78-42(30(17)18)48(66)60-35(23(3)4)50(68)74-32(20)44(62)56-37(25(7)8)52(70)76-40(28(13)14)46(64)58-34/h22-42H,1-21H3,(H,55,61)(H,56,62)(H,57,63)(H,58,64)(H,59,65)(H,60,66)/t31-,32-,33+,34-,35+,36+,37-,38-,39+,40+,41+,42+/m1/s1

| InChIKey = FCFNRCROJUBPLU-DNDCDFAIBE

| StdInChI_Ref = {{stdinchicite|changed|chemspider}}

| StdInChI = 1S/C54H90N6O18/c1-22(2)34-49(67)73-31(19)43(61)55-38(26(9)10)53(71)77-41(29(15)16)47(65)59-36(24(5)6)51(69)75-33(21)45(63)57-39(27(11)12)54(72)78-42(30(17)18)48(66)60-35(23(3)4)50(68)74-32(20)44(62)56-37(25(7)8)52(70)76-40(28(13)14)46(64)58-34/h22-42H,1-21H3,(H,55,61)(H,56,62)(H,57,63)(H,58,64)(H,59,65)(H,60,66)/t31-,32-,33-,34+,35+,36+,37-,38-,39-,40+,41+,42+/m0/s1

| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}}

| StdInChIKey = FCFNRCROJUBPLU-DNDCDFAISA-N

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| KEGG_Ref = {{keggcite|correct|kegg}}

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|Section2={{Chembox Properties

| Formula = C₅₄H₉₀N₆O₁₈

| MolarMass = 1111.32 g/mol

| Appearance = White solid

| Density =

| MeltingPtC = 190

| MeltingPt_notes =

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| Solubility =

| SolubleOther = Methanol, ethanol, ethyl acetate, petrol-ether, dichloromethane

| Solvent =

| pKa =

| pKb =

| LambdaMax = 220 nm

| Absorbance =

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| Dipole = }}

|Section3={{Chembox Structure

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|Section5={{Chembox Thermochemistry

| DeltaHf =

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|Section6={{Chembox Pharmacology

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|Section4={{Chembox Explosive

| ShockSens =

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|Section7={{Chembox Hazards

| ExternalSDS =

| MainHazards = Neurotoxicant

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| GHSPictograms = {{GHS06}}

| GHSSignalWord = Danger

| HPhrases = {{H-phrases|300|310}}

| PPhrases = {{P-phrases|262|264|270|280|301+310|302+350|310|321|322|330|361|363|405|501}}

| FlashPt =

| LD50 = 4 mg/kg (oral, rat)

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| PEL = }}

|Section8={{Chembox Related

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}}

Valinomycin is a naturally occurring dodecadepsipeptide used in the transport of potassium and as an antibiotic. Valinomycin is obtained from the cells of several Streptomyces species, S. fulvissimus being a notable one.

It is a member of the group of natural neutral ionophores because it does not have a residual charge. It consists of enantiomers D- and L-valine (Val), D-alpha-hydroxyisovaleric acid, and L-lactic acid. Structures are alternately bound via amide and ester bridges. Valinomycin is highly selective for potassium ions over sodium ions within the cell membrane.{{cite journal |author1=Lars, Rose |author2=Jenkins ATA | title=The effect of the ionophore valinomycin on biomimetic solid supported lipid DPPTE/EPC membranes | journal= Bioelectrochemistry| year=2007 | volume=70 | issue=2 | pages=387–393 | doi=10.1016/j.bioelechem.2006.05.009 | pmid=16875886}} It functions as a potassium-specific transporter and facilitates the movement of potassium ions through lipid membranes "down" the electrochemical potential gradient.{{cite journal | author=Cammann K | title=Ion-selective bulk membranes as models | journal=Top. Curr. Chem. | year=1985 | volume=128 | pages=219–258| doi=10.1007/3-540-15136-2_8 | series=Topics in Current Chemistry | isbn=978-3-540-15136-4 }} The stability constant K for the potassium-valinomycin complex is nearly 100,000 times larger than that of the sodium-valinomycin complex.{{cite journal|vauthors=Rose MC, Henkens RW |title=Stability of sodium and potassium complexes of valinomycin|journal=Biochimica et Biophysica Acta (BBA) - General Subjects|year=1974|volume=372|issue=2|pages=426–435|doi=10.1016/0304-4165(74)90204-9}}

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 an extremely 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.{{Cite web | publisher = Government Printing Office | title = 40 C.F.R.: Appendix A to Part 355—The List of Extremely Hazardous Substances and Their Threshold Planning Quantities | url = http://edocket.access.gpo.gov/cfr_2008/julqtr/pdf/40cfr355AppA.pdf | edition = July 1, 2008 | access-date = October 29, 2011 | archive-date = February 25, 2012 | archive-url = https://web.archive.org/web/20120225051612/http://edocket.access.gpo.gov/cfr_2008/julqtr/pdf/40cfr355AppA.pdf | url-status = live }}

Structure

Valinomycin is a dodecadepsipeptide, that is, it is made of twelve alternating amino acids and esters to form a macrocyclic molecule. The twelve carbonyl groups are essential for the binding of metal ions, and also for solvation in polar solvents. The isopropyl and methyl groups are responsible for solvation in nonpolar solvents.

{{cite journal |vauthors=Thompson M, Krull UJ|title=The electroanalytical response of the bilayer lipid membrane to valinomycin: membrane cholesterol content | journal=Anal. Chim. Acta | year=1982 | volume=141 | pages=33–47 | doi=10.1016/S0003-2670(01)95308-5|bibcode=1982AcAC..141...33T }} 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.

Applications

Valinomycin was recently reported to be the most potent agent against severe acute respiratory-syndrome coronavirus (SARS-CoV) in infected Vero E6 cells.{{Cite journal|last1=Zhang|first1=Dong|last2=Ma|first2=Zhi|last3=Chen|first3=Hanchi|last4=Lu|first4=Yuele|last5=Chen|first5=Xiaolong|date=October 2020|title=Valinomycin as a potential antiviral agent against coronaviruses: A review|journal=Biomedical Journal|volume=43|issue=5|pages=414–423|doi=10.1016/j.bj.2020.08.006|pmid=33012699|pmc=7417921|issn=2319-4170|doi-access=free}} Valinomycin has been shown to inhibit completely vaccinia virus in cell based assay in human cell line.{{Cite journal |last1=Witwit |first1=Haydar |last2=Cubitt |first2=Beatrice |last3=Khafaji |first3=Roaa |last4=Castro |first4=Esteban M. |last5=Goicoechea |first5=Miguel |last6=Lorenzo |first6=Maria M. |last7=Blasco |first7=Rafael |last8=Martinez-Sobrido |first8=Luis |last9=de la Torre |first9=Juan C. |date=January 2025 |title=Repurposing Drugs for Synergistic Combination Therapies to Counteract Monkeypox Virus Tecovirimat Resistance |journal=Viruses |language=en |volume=17 |issue=1 |pages=92 |doi=10.3390/v17010092 |doi-access=free |issn=1999-4915|pmc=11769280 }}

Valinomycin acts as a nonmetallic isoforming agent in potassium selective electrodes.{{cite journal |vauthors=Safiulina D, Veksler V, Zharkovsky A, Kaasik A | title=Loss of mitochondrial membrane potential is associated with increase in mitochondrial volume: physiological role in neurones | journal= J. Cell. Physiol. | year=2006 | volume=206 | issue=2 | pages=347–353 | doi=10.1002/jcp.20476 | pmid= 16110491| s2cid=34918061 }}{{Cite web |url=http://www.sigmaaldrich.com/etc/medialib/docs/Sigma/Instructions/k_potassium.Par.0001.File.tmp/k_potassium.pdf |title=Potassium ionophore Bulletin |access-date=2009-05-19 |archive-date=2012-03-15 |archive-url=https://web.archive.org/web/20120315145943/http://www.sigmaaldrich.com/etc/medialib/docs/Sigma/Instructions/k_potassium.Par.0001.File.tmp/k_potassium.pdf |url-status=live }}

This ionophore is used to study membrane vesicles, where it may be selectively applied by experimental design to reduce or eliminate the electrochemical gradient across a membrane.{{citation needed|reason=Previous ref was not a valid URL|date=August 2019}}

References

External links

[http://www.state.nj.us/health/eoh/rtkweb/2850.pdf Chemical Safety Regulations] from New Jersey Department of Health.
[http://www.scorecard.org/chemical-profiles/summary.tcl?edf_substance_id=2001-95-8 Health information on Scorecard] {{Webarchive|url=https://web.archive.org/web/20050518201502/http://www.scorecard.org/chemical-profiles/summary.tcl?edf_substance_id=2001-95-8 |date=2005-05-18 }}.
[http://www.fermentek.com/product/valinomycin Valinomycin] from Fermentek.
{{PPDB|2586}}

Category:Cyclic peptides

Category:Ionophores

Category:Depsipeptides

Category:Mitochondrial toxins