Radicicol: Difference between revisions
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Script assisted update of identifiers from ChemSpider, CommonChemistry and FDA for the Chem/Drugbox validation project - Updated: InChI1->InChI StdInChI StdInChIKey. |
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| ImageFile = Radicicol Winssinger et al.svg |
| ImageFile = Radicicol Winssinger et al.svg |
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| ImageSize = 250 |
| ImageSize = 250 |
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| PIN = (1a''R'',2''E'',4''E'',14''R'',15a''R'')-8-Chloro-9,11-dihydroxy-14-methyl-1a,14,15,15a-tetrahydro-6''H''-oxireno[''e''][2]benzoxacyclotetradecine-6,12(7''H'')-dione |
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| OtherNames = |
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|Section1={{Chembox Identifiers |
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| Abbreviations = |
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| ChemSpiderID_Ref = {{chemspidercite|changed|chemspider}} |
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| SMILES = C[C@@H]1C[C@@H]2[C@H](O2)/C=C\C=C\C(=O)Cc3c(c(cc(c3Cl)O)O)C(=O)O1 |
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| StdInChI_Ref = {{stdinchicite|changed|chemspider}} |
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| StdInChIKey_Ref = {{stdinchicite|changed|chemspider}} |
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| CASNo = 12772-57-5 |
| CASNo = 12772-57-5 |
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| CASNo_Ref ={{cascite| |
| CASNo_Ref = {{cascite|correct|CAS}} |
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| UNII_Ref = {{fdacite|correct|FDA}} |
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| UNII = I60EH8GECX |
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| EINECS = |
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| PubChem = 6323491 |
| PubChem = 6323491 |
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| ChEMBL_Ref = {{ebicite|changed|EBI}} |
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| ChEMBL = 453386 |
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| SMILES = O=C1\C=C\C=C/C3OC3CC(C)OC(=O)c2c(O)cc(O)c(Cl)c2C1 |
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| InChI = |
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| ChEBI_Ref = {{ebicite|changed|EBI}} |
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| ChEBI = 556075 |
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| ATCCode = }} |
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|Section2={{Chembox Properties |
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| MolarMass = |
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| C=18|H=17|Cl=1|O=6 |
| C=18 | H=17 | Cl=1 | O=6 |
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| Appearance = |
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|Section4={{Chembox Thermochemistry |
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| DeltaHf = |
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|Section6={{Chembox Explosive |
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| ShockSens = |
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| REFactor = }} |
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|Section7={{Chembox Hazards |
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| ExternalSDS = |
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| EUClass = |
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| GHS_ref = |
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| FlashPt = |
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| AutoignitionPt = |
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| ExploLimits = |
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| PEL = }} |
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|Section8={{Chembox Related |
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| OtherAnions = |
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'''Radicicol''', also known as '''monorden''', is a natural product that binds to [[Hsp90]] (Heat Shock Protein 90) and alters its function. HSP90 client proteins play important roles in the regulation of the cell cycle, cell growth, cell survival, [[apoptosis]], [[angiogenesis]] and [[oncogenesis]]. |
'''Radicicol''', also known as '''monorden''', is a natural product that binds to [[Hsp90]] (Heat Shock Protein 90) and alters its function. HSP90 client proteins play important roles in the regulation of the cell cycle, cell growth, cell survival, [[apoptosis]], [[angiogenesis]] and [[oncogenesis]]. |
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== Biosynthesis == |
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Biosynthesis of radicicol has been best studied in ''[[Pochonia chlamydosporia]]'', in which the majority of the core structure is produced in vivo through iterative type I [[polyketide synthases]].<ref>{{cite journal | doi = 10.1074/jbc.M110.183574 | volume=285 | title=Insights into Radicicol Biosynthesis via Heterologous Synthesis of Intermediates and Analogs | journal=Journal of Biological Chemistry | pages=41412–41421 | pmid=20961859 | pmc=3009867 | vauthors=Zhou H, Qiao K, Gao Z, Vederas JC, Tang Y| year=2010 | issue=53 | doi-access=free }}</ref> This structure produced is the earliest intermediate in the radicicol biosynthesis, monocillin II. This intermediate is transformed to radicicol through halogenation and epoxide formation performed by RadH and RadP respectively.<ref name=Wang>{{cite journal | doi = 10.1016/j.chembiol.2008.10.006 | volume=15 | title=Functional Characterization of the Biosynthesis of Radicicol, an Hsp90 Inhibitor Resorcylic Acid Lactone from Chaetomium chiversii | journal= Chemistry & Biology| year=2008 | pages=1328–1338| doi-access=free | last1=Wang | first1=Shuhao | last2=Xu | first2=Yuquan | last3=Maine | first3=Erin A. | last4=Wijeratne | first4=E.M. Kithsiri | last5=Espinosa-Artiles | first5=Patricia | last6=Gunatilaka | first6=A.A. Leslie | last7=Molnár | first7=István | issue=12 | pmid=19101477 }}</ref> These enzymes are coded by the genes Rdc2 and Rdc4 in the pathway, and removing either of these results in a product that has the monocillin II core, but does not have either the epoxide or halogen added.<ref name=Wang/> |
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[[File:Proposed Radicicol Biosynthetic Pathway.png|thumb|400px|left|Proposed biosynthetic pathway of Radicicol.]]{{clear left}} |
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== See also == |
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* [[Geldanamycin]] |
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== References == |
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<references /> |
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==Further reading== |
==Further reading== |
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*{{cite journal | |
*{{cite journal |vauthors=Winssinger N, Barluanga S |title=Chemistry and biology of resorcylic acid lactones |journal=Chem Commun |volume= 13|issue=1 |pages=22–36 |date=January 2007 |doi=10.1039/B610344H |pmid=17279252 }} Review of the chemistry and biology of resorcylic acid lactones, including radicicol. |
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[[Category:Epoxides]] |
[[Category:Epoxides]] |
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[[Category:Macrolides]] |
[[Category:Macrolides]] |
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[[Category:Halogen-containing natural products]] |
[[Category:Halogen-containing natural products]] |
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[[Category:Polyketides]] |
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[[Category:Chloroarenes]] |
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{{biochem-stub}} |
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Latest revision as of 14:19, 23 December 2023
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| Names | |
|---|---|
| Preferred IUPAC name
(1aR,2E,4E,14R,15aR)-8-Chloro-9,11-dihydroxy-14-methyl-1a,14,15,15a-tetrahydro-6H-oxireno[e][2]benzoxacyclotetradecine-6,12(7H)-dione | |
| Identifiers | |
3D model (JSmol)
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| ChEBI | |
| ChEMBL | |
| ChemSpider | |
| ECHA InfoCard | 100.170.695 |
PubChem CID
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| UNII | |
CompTox Dashboard (EPA)
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| Properties | |
| C18H17ClO6 | |
| Molar mass | 364.78 g·mol−1 |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Radicicol, also known as monorden, is a natural product that binds to Hsp90 (Heat Shock Protein 90) and alters its function. HSP90 client proteins play important roles in the regulation of the cell cycle, cell growth, cell survival, apoptosis, angiogenesis and oncogenesis.
Biosynthesis[edit]
Biosynthesis of radicicol has been best studied in Pochonia chlamydosporia, in which the majority of the core structure is produced in vivo through iterative type I polyketide synthases.[1] This structure produced is the earliest intermediate in the radicicol biosynthesis, monocillin II. This intermediate is transformed to radicicol through halogenation and epoxide formation performed by RadH and RadP respectively.[2] These enzymes are coded by the genes Rdc2 and Rdc4 in the pathway, and removing either of these results in a product that has the monocillin II core, but does not have either the epoxide or halogen added.[2]
See also[edit]
References[edit]
- ^ Zhou H, Qiao K, Gao Z, Vederas JC, Tang Y (2010). "Insights into Radicicol Biosynthesis via Heterologous Synthesis of Intermediates and Analogs". Journal of Biological Chemistry. 285 (53): 41412–41421. doi:10.1074/jbc.M110.183574. PMC 3009867. PMID 20961859.
- ^ a b Wang, Shuhao; Xu, Yuquan; Maine, Erin A.; Wijeratne, E.M. Kithsiri; Espinosa-Artiles, Patricia; Gunatilaka, A.A. Leslie; Molnár, István (2008). "Functional Characterization of the Biosynthesis of Radicicol, an Hsp90 Inhibitor Resorcylic Acid Lactone from Chaetomium chiversii". Chemistry & Biology. 15 (12): 1328–1338. doi:10.1016/j.chembiol.2008.10.006. PMID 19101477.
Further reading[edit]
- Winssinger N, Barluanga S (January 2007). "Chemistry and biology of resorcylic acid lactones". Chem Commun. 13 (1): 22–36. doi:10.1039/B610344H. PMID 17279252. Review of the chemistry and biology of resorcylic acid lactones, including radicicol.