Squalestatin A
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| Category | Enzyme inhibitors |
| Catalog number | BBF-03466 |
| CAS | 142561-96-4 |
| Molecular Weight | 690.73 |
| Molecular Formula | C35H46O14 |
| Purity | >98% by HPLC |
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Description
It is a squalene synthase inhibitor produced by the strain of Phoma sp. C2932. It inhibits squalene synthase in mammalian (rat liver) and Candida albicans, and has a broad-spectrum antifungal effect.
Specification
| Related CAS | 144541-82-2 (trisodium salt) |
| Synonyms | Zaragozic acid A; squalestatin 1; Squalestatin; L-erythro-L-glycero-D-altro-7-Trideculo-7,4-furanosonic acid, 2,7-anhydro-3,4-di-C-carboxy-8,9,10,12,13-pentadeoxy-10-methylene-12-(phenylmethyl)-, 11-acetate 5-(4,6-dimethyl-2-octenoate), (5(2E,4S,6S),7S)-; L-erythro-L-glycero-D-altro-7-Trideculo-7,4-furanosonic acid, 2,7-anhydro-3,4-di-C-carboxy-8,9,10,12,13-pentadeoxy-10-methylene-12-(phenylmethyl)-, 11-acetate 5-[(2E,4S,6S)-4,6-dimethyl-2-octenoate], (7S)-; Squalestatin S1 |
| Storage | Store at-20°C |
| IUPAC Name | (1S,3S,4S,5R,6R,7R)-1-[(4S,5R)-4-acetyloxy-5-methyl-3-methylidene-6-phenylhexyl]-6-[(E,4S,6S)-4,6-dimethyloct-2-enoyl]oxy-4,7-dihydroxy-2,8-dioxabicyclo[3.2.1]octane-3,4,5-tricarboxylic acid |
| Canonical SMILES | CCC(C)CC(C)C=CC(=O)OC1C(C2(OC(C(C1(O2)C(=O)O)(C(=O)O)O)C(=O)O)CCC(=C)C(C(C)CC3=CC=CC=C3)OC(=O)C)O |
| InChI | InChI=1S/C35H46O14/c1-7-19(2)17-20(3)13-14-25(37)47-28-27(38)33(48-29(30(39)40)34(45,31(41)42)35(28,49-33)32(43)44)16-15-21(4)26(46-23(6)36)22(5)18-24-11-9-8-10-12-24/h8-14,19-20,22,26-29,38,45H,4,7,15-18H2,1-3,5-6H3,(H,39,40)(H,41,42)(H,43,44)/b14-13+/t19-,20+,22+,26+,27+,28+,29+,33-,34+,35-/m0/s1 |
| InChI Key | DFKDOZMCHOGOBR-NCSQYGPNSA-N |
| Source | Unidentified fungus |
Properties
| Appearance | White Powder |
| Antibiotic Activity Spectrum | Fungi; Yeast |
| Boiling Point | 850.1±65.0°C (Predicted) |
| Density | 1.35±0.1 g/cm3 (Predicted) |
| Solubility | Soluble in Chloroform, Acetonitrile |
Reference Reading
1. In vitro kinetic study of the squalestatin tetraketide synthase dehydratase reveals the stereochemical course of a fungal highly reducing polyketide synthase
Alan Scott, Emma Liddle, David Ivison, Li-Chen Han, Christine L Willis, Thomas J Simpson, Russell J Cox Chem Commun (Camb) . 2017 Feb 4;53(10):1727-1730. doi: 10.1039/c6cc10172k.
Six potential diketide substrates for the squalestatin tetraketide synthase (SQTKS) dehydratase (DH) domain were synthesised as N-acetyl cysteamine thiolesters (SNAC) and tested in kinetic assays as substrates with an isolated DH domain. 3R-3-hydroxybutyryl SNAC 3R-16 was turned over by the enzyme, but its enantiomer was not. Of the four 2-methyl substrates only 2R,3R-2-methyl-3-hydroxybutyryl SNAC 2R,3R-8 was a substrate. Combined with stereochemical information from the isolated SQTKS enoyl reductase (ER) domain, our results provide a near complete stereochemical description of the first cycle of beta-modification reactions of a fungal highly reducing polyketide synthase (HR-PKS). The results emphasise the close relationship between fungal HR-PKS and vertebrate fatty acid synthases (vFAS).
2. Squalestatin is an inhibitor of carotenoid biosynthesis in Plasmodium falciparum
Alejandro M Katzin, Heloisa B Gabriel, Gerhard Wunderlich, Mauro F Azevedo, Marcia F Silva, Emília A Kimura Antimicrob Agents Chemother . 2015;59(6):3180-8. doi: 10.1128/AAC.04500-14.
The increasing resistance of malaria parasites to almost all available drugs calls for the characterization of novel targets and the identification of new compounds. Carotenoids are polyisoprenoids from plants, algae, and some bacteria, and they are biosynthesized by Plasmodium falciparum but not by mammalian cells. Biochemical and reverse genetics approaches were applied to demonstrate that phytoene synthase (PSY) is a key enzyme for carotenoid biosynthesis in P. falciparum and is essential for intraerythrocytic growth. The known PSY inhibitor squalestatin reduces biosynthesis of phytoene and kills parasites during the intraerythrocytic cycle. PSY-overexpressing parasites showed increased biosynthesis of phytoene and its derived product phytofluene and presented a squalestatin-resistant phenotype, suggesting that this enzyme is the primary target of action of this drug in the parasite.
3. Squalestatin alters the intracellular trafficking of a neurotoxic prion peptide
James Brewer, Clive Bate, Alun Williams, Ronald Boshuizen, Rona Wilson BMC Neurosci . 2007 Nov 22;8:99. doi: 10.1186/1471-2202-8-99.
Background:Neurotoxic peptides derived from the protease-resistant core of the prion protein are used to model the pathogenesis of prion diseases. The current study characterised the ingestion, internalization and intracellular trafficking of a neurotoxic peptide containing amino acids 105-132 of the murine prion protein (MoPrP105-132) in neuroblastoma cells and primary cortical neurons.Results:Fluorescence microscopy and cell fractionation techniques showed that MoPrP105-132 co-localised with lipid raft markers (cholera toxin and caveolin-1) and trafficked intracellularly within lipid rafts. This trafficking followed a non-classical endosomal pathway delivering peptide to the Golgi and ER, avoiding classical endosomal trafficking via early endosomes to lysosomes. Fluorescence resonance energy transfer analysis demonstrated close interactions of MoPrP105-132 with cytoplasmic phospholipase A2 (cPLA2) and cyclo-oxygenase-1 (COX-1), enzymes implicated in the neurotoxicity of prions. Treatment with squalestatin reduced neuronal cholesterol levels and caused the redistribution of MoPrP105-132 out of lipid rafts. In squalestatin-treated cells, MoPrP105-132 was rerouted away from the Golgi/ER into degradative lysosomes. Squalestatin treatment also reduced the association between MoPrP105-132 and cPLA2/COX-1.Conclusion:As the observed shift in peptide trafficking was accompanied by increased cell survival these studies suggest that the neurotoxicity of this PrP peptide is dependent on trafficking to specific organelles where it activates specific signal transduction pathways.
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Bio Calculators
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
* Total Molecular Weight:
g/mol
Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳
