| Revision as of 10:46, 20 February 2012 editBeetstra (talk | contribs)Edit filter managers, Administrators172,031 edits Saving copy of the {{chembox}} taken from revid 442174255 of page Thioflavin for the Chem/Drugbox validation project (updated: 'CASNo'). |
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{{ambox | text = This page contains a copy of the infobox ({{tl|chembox}}) taken from revid of page ] with values updated to verified values.}} |
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{{chembox |
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{{chembox |
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| Verifiedfields = changed |
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| verifiedrevid = 442173219 |
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| verifiedrevid = 477863380 |
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| Name = Thioflavin T |
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| Name = Thioflavin T |
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| ImageFile = Thioflavin T.png |
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| ImageFile = Thioflavin T.svg |
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| ImageSize = |
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| ImageSize = |
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| ImageFile1 = Thioflavin-T-3D-balls.png |
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| ImageFile1 = Thioflavin-T-3D-balls.png |
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| ImageSize1 = 200px |
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| ImageSize1 = 200px |
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| IUPACName = <span style="white-space:nowrap;">4-(3,6-dimethyl-1,3-benzothiazol-3<br />-ium-2-yl)-N,N-dimethylaniline chloride</span> |
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| PIN = 2--3,6-dimethyl-1,3-benzothiazol-3-ium chloride |
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| OtherNames = |
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| OtherNames = |
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| Section1 = {{Chembox Identifiers |
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|Section1={{Chembox Identifiers |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} |
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| ChemSpiderID = 16062 |
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| ChemSpiderID = 16062 |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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| ChEMBL_Ref = {{ebicite|correct|EBI}} |
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| ChEMBL = 224392 |
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| ChEMBL = 224392 |
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| ChEBI_Ref = {{ebicite|changed|EBI}} |
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| ChEBI = 88013 |
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| ChEMBL2_Ref = {{ebicite|correct|EBI}} |
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| ChEMBL2 = 224392 |
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| ChEMBL2 = 224392 |
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| InChI = 1/C17H19N2S.ClH/c1-12-5-10-15-16(11-12)20-17(19(15)4)13-6-8-14(9-7-13)18(2)3;/h5-11H,1-4H3;1H/q+1;/p-1 |
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| InChI = 1/C17H19N2S.ClH/c1-12-5-10-15-16(11-12)20-17(19(15)4)13-6-8-14(9-7-13)18(2)3;/h5-11H,1-4H3;1H/q+1;/p-1 |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} |
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| StdInChIKey = JADVWWSKYZXRGX-UHFFFAOYSA-M |
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| StdInChIKey = JADVWWSKYZXRGX-UHFFFAOYSA-M |
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| CASNo = <!-- blanked - oldvalue: 2390-54-7 --> |
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| CASNo = 2390-54-7 |
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| CASNo_Ref = {{cascite|correct|CAS}} |
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| PubChem = 16953 |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| SMILES = .s2c1cc(ccc1(c2c3ccc(N(C)C)cc3)C)C |
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| UNII = CAX9SG0II0 |
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| PubChem = 16953 |
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| SMILES = .s2c1cc(ccc1(c2c3ccc(N(C)C)cc3)C)C |
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| Section2 = {{Chembox Properties |
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|Section2={{Chembox Properties |
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| Formula = C<sub>17</sub>H<sub>19</sub>ClN<sub>2</sub>S |
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| Formula = C<sub>17</sub>H<sub>19</sub>ClN<sub>2</sub>S |
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| MolarMass = 318.86 g/mol |
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| MolarMass = 318.86 g/mol |
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| Section3 = {{Chembox Hazards |
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|Section3={{Chembox Hazards |
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| MainHazards = |
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| FlashPt = |
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'''Thioflavins''' are ]s that are available as at least two compounds, namely '''Thioflavin T''' and '''Thioflavin S'''. Both are used for ] staining and ] studies of protein aggregation.<ref name="Review">{{cite journal|vauthors=Biancalana M, Koide S|date=July 2010|title=Molecular mechanism of Thioflavin-T binding to amyloid fibrils|journal=Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics|volume=1804|issue=7|pages=1405–12|doi=10.1016/j.bbapap.2010.04.001|pmc=2880406|pmid=20399286}}</ref> In particular, these dyes have been used since 1989 to investigate amyloid formation.<ref name="gade">{{cite journal|last1=Gade Malmos|first1=Kirsten|last2=Blancas-Mejia|first2=Luis M.|last3=Weber|first3=Benedikt|last4=Buchner|first4=Johannes|last5=Ramirez-Alvarado|first5=Marina|last6=Naiki|first6=Hironobu|last7=Otzen|first7=Daniel|year=2017|title=THT 101: A primer on the use of thioflavin T to investigate amyloid formation|journal=Amyloid|volume=24|issue=1|pages=1–16|doi=10.1080/13506129.2017.1304905|pmid=28393556|doi-access=free}}</ref> They are also used in biophysical studies of the electrophysiology of bacteria.<ref name="bacteria">{{cite journal|vauthors=Prindle A, Liu J, Asally M, Ly S, Garcia-Ojalvo J, Süel GM|date=November 2015|title=Ion channels enable electrical communication in bacterial communities|journal=Nature|volume=527|issue=7576|pages=59–63|bibcode=2015Natur.527...59P|doi=10.1038/nature15709|pmc=4890463|pmid=26503040}}</ref> Thioflavins are ], ], and acutely toxic, causing serious eye damage.<ref>{{cite web|title=Thioflavin T|url=https://pubchem.ncbi.nlm.nih.gov/compound/16953|publisher=National Center for Biotechnology Information|agency=PubChem}}</ref> Thioflavin T has been used in research into ] and other ]. |
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==Thioflavin T== |
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Thioflavin T (Basic Yellow 1, Methylene yellow, CI 49005, or ThT) is a ] salt obtained by the methylation of ] with ] in the presence of ]. The dye is widely used to visualize and quantify the presence of misfolded ] aggregates called ], both '']'' and '']'' (e.g., ] composed of ] found in the brains of ] patients).<ref name="Review"/> |
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When it binds to ]-rich structures, such as those in amyloid aggregates, the dye displays enhanced ] and a characteristic ] of its ].<ref name="methods">H. LeVine III, ''Methods in Enzymology.'' '''309''', 274 (1999)</ref><ref name="Minna">{{cite journal | vauthors = Groenning M | title = Binding mode of Thioflavin T and other molecular probes in the context of amyloid fibrils-current status | journal = Journal of Chemical Biology | volume = 3 | issue = 1 | pages = 1–18 | date = March 2010 | pmid = 19693614 | pmc = 2816742 | doi = 10.1007/s12154-009-0027-5 }}</ref> Additional studies also consider ] changes as result of the interaction with double stranded DNA.<ref name="DNA">{{cite journal | vauthors = Ilanchelian M, Ramaraj R | year = 2004 | title = Emission of thioflavin T and its control in the presence of DNA | journal = Journal of Photochemistry and Photobiology A: Chemistry | volume = 162 | issue = 1 | pages = 129–137 | doi=10.1016/s1010-6030(03)00320-4| bibcode = 2004JPPA..162..129I }}</ref> This change in fluorescent behavior can be caused by many factors that affect the ] ] of thioflavin T, including binding to a rigid, highly-ordered nanopocket, and specific chemical interactions between thioflavin T and the nanopocket.<ref name="wolfe">{{cite journal | vauthors = Wolfe LS, Calabrese MF, Nath A, Blaho DV, Miranker AD, Xiong Y | title = Protein-induced photophysical changes to the amyloid indicator dye thioflavin T | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 107 | issue = 39 | pages = 16863–8 | date = September 2010 | pmid = 20826442 | pmc = 2947910 | doi = 10.1073/pnas.1002867107 | bibcode = 2010PNAS..10716863W | doi-access = free }}</ref><ref name="IJQC">{{cite journal | vauthors = Biancardi A, Biver T, Mennucci B | year = 2017 | title = Fluorescent dyes in the context of DNA-binding: The case of Thioflavin T | journal = Int. J. Quantum Chem. | volume = 117 | issue = 8| pages = e25349 | doi = 10.1002/qua.25349 }}</ref> |
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Prior to binding to an amyloid fibril, thioflavin T emits weakly around 427 nm. Quenching effects of the nearby excitation peak at 450 nm is suspected to play a role in minimizing emissions. |
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When excited at 450 nm, thioflavin T produces a strong fluorescence signal at approximately 482 nm upon binding to amyloids. Thioflavin T molecule consists of a benzylamine and a benzothiazole ring connected through a carbon-carbon bond. These two rings can rotate freely when the molecule is in solution. The free rotation of these rings results in quenching of any excited state generated by photon excitation. However, when thioflavin T binds to amyloid fibrils, the two rotational planes of the two rings become immobilized and therefore, this molecule can maintain its excited state.<ref name="Review"/> |
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Thioflavin T fluorescence is often used as a diagnostic of amyloid structure, but it is not perfectly specific for amyloid. Depending on the particular protein and experimental conditions, thioflavin T may<ref name="wolfe" /> or may not<ref name="pmid8453378">{{cite journal | vauthors = LeVine H | title = Thioflavine T interaction with synthetic Alzheimer's disease beta-amyloid peptides: detection of amyloid aggregation in solution | journal = Protein Science | volume = 2 | issue = 3 | pages = 404–10 | date = March 1993 | pmid = 8453378 | pmc = 2142377 | doi = 10.1002/pro.5560020312 }}</ref> undergo a spectroscopic change upon binding to precursor monomers, small oligomers, unaggregated material with a high ] content, or even ]-rich proteins. Conversely, some amyloid fibers do not affect thioflavin T fluorescence,<ref>{{cite journal | vauthors = Cloe AL, Orgel JP, Sachleben JR, Tycko R, Meredith SC | title = The Japanese mutant Aβ (ΔE22-Aβ(1-39)) forms fibrils instantaneously, with low-thioflavin T fluorescence: seeding of wild-type Aβ(1-40) into atypical fibrils by ΔE22-Aβ(1-39) | journal = Biochemistry | volume = 50 | issue = 12 | pages = 2026–39 | date = March 2011 | pmid = 21291268 | pmc = 3631511 | doi = 10.1021/bi1016217 }}</ref> raising the prospect of ] results. |
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{{wide image|Thioflavin T bound to amyloid-like oligomer.png|720px|alt=X-ray crystal structure of thioflavin T bound to an amyloid-like oligomer of β2 microglobulin|Structure of thioflavin T bound to an ]-like oligomer of ] (in gray), in a complex that displays enhanced and ]ed fluorescence. Many factors that shift the ] charge from the dimethylaminobenzyl portion of thioflavin T (in blue) to the benzothiazole portion (in red), including binding to rigid, highly-ordered amyloid aggregates, can produce this 'positive' thioflavin T signal.<ref name="wolfe"/>}}<br />{{wide image|Merge-Thio-Ab9-2+text copy.jpg|720px|Thioflavin S stain (left in green) and ] antibody immunocytochemistry (right) on adjacent sections of the hippocampus of a patient suffering from ]. Thioflavin S binds both ] (SP) and ] (NFT), the two characteristic cortical lesions of Alzheimer's. Amyloid beta is a peptide derived from the ] which is only found in senile plaques, and so only plaques are visible in the right hand image. The left image also has a red signal which exactly superimposes the green signal in ] granules (LP), which are autofluorescent inclusions derived from ] which accumulate in the human brain during normal aging.}} |
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In adult ''C. elegans'', exposure to thioflavin T results "in a profoundly extended lifespan and slowed aging" at some levels, but decreased lifespan at higher levels.<ref name="pmid21451522">{{cite journal | vauthors = Alavez S, Vantipalli MC, Zucker DJ, Klang IM, Lithgow GJ | title = Amyloid-binding compounds maintain protein homeostasis during ageing and extend lifespan | journal = Nature | volume = 472 | issue = 7342 | pages = 226–9 | date = April 2011 | pmid = 21451522 | pmc = 3610427 | doi = 10.1038/nature09873 | bibcode = 2011Natur.472..226A }}</ref> |
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==Thioflavin S== |
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Thioflavin S is a homogenous mixture of compounds that results from the methylation of dehydrothiotoluidine with ]. It is also used to stain amyloid plaques. Like thioflavin T it binds to ]s but not monomers and gives a distinct increase in fluorescence emission. However unlike thioflavin T, it does not produce a characteristic shift in the excitation or emission spectra.<ref name="methods"/> This latter characteristic of thioflavin S results in high background fluorescence, making it unable to be used in quantitative measurements of fibril solutions.<ref name="methods"/> Another dye that is used to identify amyloid structure is ]. |
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==See also== |
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* ] |
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== References == |
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{{reflist}} |
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{{Stains}} |
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