Exciton-coupled circular dichroism (ECCD) in acyclic hydroxylated dienes: A sensitive method for the direct stereochemical assignment of lipoxygenase products

Schneider, Claus; Schreier, Peter; Humpf, Hans‐Ulrich

doi:10.1002/(sici)1520-636x(1997)9:5/6<563::aid-chir25>3.0.co;2-l

Cited by 27 publications

(5 citation statements)

References 21 publications

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“…It was surprising to find that the positions of Br and Cl in 6 and 7 are reversed at C-8 and C-9 and their relative configurations inverted, respectively. With the exception of 10 , mollenynes contain a C-7 allylic secondary hydroxyl group; presumably this is introduced through a cytochrome P 450 mediated enzymatic oxidation of an unsaturated precursor, as is typical in the biosynthesis of similar allylic alcohols . Assuming both 6 and 7 share the 7 S absolute configuration (derived experimentally for 6 ), the implied relative configurations at C-8 and C-9 in 7 are epimeric to those stereocenters in 6 .…”

Section: Resultsmentioning

confidence: 99%

Mollenynes B–E from the Marine Sponge Spirastrella mollis. Band-Selective Heteronuclear Single Quantum Coherence for Discrimination of Bromo–Chloro Regioisomerism in Natural Products

2015

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Four new chlorobromohydrins, mollenynes B-E, were isolated from the marine sponge Spirastrella mollis collected from Hogsty Reef, Bahamas. Their structures were elucidated by integrated analysis of NMR, MS, and computational methods. A high-resolution band-selective HSQC experiment was developed to identify (13)C NMR signals in samples at the nanomole-scale that arise from Cl-substituted (13)C by exploiting the (35)Cl/(37)Cl isotope shift.

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Section: Resultsmentioning

confidence: 99%

Mollenynes B–E from the Marine Sponge Spirastrella mollis. Band-Selective Heteronuclear Single Quantum Coherence for Discrimination of Bromo–Chloro Regioisomerism in Natural Products

2015

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“…Therefore, the stereoconfiguration of the 8-hydroxyl was determined by CD spectroscopy (9,10). This method requires the presence of two suitable chromophores at the asymmetric carbon, one being provided by the 9,10 double bond and the other introduced at C-8 by derivatization to the benzoate ester.…”

Section: Resultsmentioning

confidence: 99%

The lipoxygenase gene ALOXE3 implicated in skin differentiation encodes a hydroperoxide isomerase

Schneider

Boeglin

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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138

152

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Herein we identify a logical link of the biochemistry to the genetics. eLOX3 functions as a hydroperoxide isomerase (epoxyalcohol synthase) by using the product of 12R-LOX as the preferred substrate. 12R-Hydroperoxyeicosatetraenoic acid (12R-HPETE) is converted to 8R-hydroxy-11R,12R-epoxyeicosa-5Z,9E,14Z-trienoic acid, one of the isomers of hepoxilin A 3, and to 12-ketoeicosatetraenoic acid in a 2:1 ratio. Other hydroperoxides, including 8R-HPETE, 12S-HPETE, and 15S-HPETE, as well as the 13S-and 13R-hydroperoxides of linoleic acid are converted less efficiently. Mass spectrometric analysis of the epoxyalcohol formed from [ 18 O]15S-HPETE showed that both hydroperoxy oxygens are retained in the product. We propose that the ferrous form of eLOX3 initiates a redox cycle, unprecedented among LOX in being autocatalytic, in which the hydroperoxy substrate is isomerized to the epoxyalcohol or keto product. Our results provide strong biochemical evidence for a functional linkage of 12R-LOX and eLOX3 and clues into skin biochemistry and the etiology of ichthyosiform diseases in humans. L ipoxygenases (LOXs) are a family of nonheme ironcontaining enzymes that oxygenate unsaturated fatty acids such as arachidonic acid to specific hydroperoxide products (1). These may be metabolized further to various bioactive lipid mediators including leukotrienes, lipoxins, hydroxyeicosatetraenoic acids (HETEs), and hepoxilins (2). Although LOX enzymes are catalytically active with free fatty acid substrates, some will also oxygenate esterified substrates such as the phospholipid or cholesterol esters. LOX metabolites play important roles in cell signaling or modification of membrane structures (1, 3).There are five active LOXs found in human beings: 5-LOX, 12S-LOX, 12R-LOX, 15-LOX-1, and 15-LOX-2. A sixth gene family member, epidermal LOX type 3 (eLOX3, gene symbol ALOXE3) was described first in the mouse (4), and in humans in 2001 (5). The amino acid sequence of human eLOX3 shows the closest similarity to 12R-LOX (54% identity) and 15-LOX-2 (51%). It contains the characteristic well conserved amino acid residues found in all LOXs including the putative iron-binding ligands and additional structure-determining residues. These features clearly indicate that eLOX3 belongs to the LOX gene family. The question of the catalytic activity of eLOX3, nonetheless, has remained elusive. No enzymatic activity has been detected by using linoleic or arachidonic acids, the prototypical C18 and C20 LOX substrates, nor with methyl arachidonate or cholesteryl arachidonate (4). In the first section of Results we confirm and extend these findings.Studies in humans and the mouse indicate that eLOX3 has a limited scope of tissue expression, being mainly confined to keratinized epithelia such as skin. From PCR evidence it seems to be coexpressed in tissues that express the 12R-LOX (5). A functional relationship to skin pathophysiology is strongly suggested by a recent genetic study reporting that eLOX3 or 12R-LOX are mutated in six families affected by nonbul...

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“…Koshino et al (28) isolated four different (R)-hydroxy fatty acids with a vicinal monoene, and with each of the methyl esters they obtained a negative specific rotation at the α D line of Na. Therefore, it would appear that interpretation of the CD of DHOE by Knothe et al (4) is suspect, and a more facile interpretation of DHOE CD might be accomplished by using the exciton-coupled CD method with hydroxyls derivatized with either p-bromobenzoate (29) or 2-naphthoate (30).…”

Section: Resultsmentioning

confidence: 99%

All (S) stereoconfiguration of 7,10‐dihydroxy‐8(E)‐octadecenoic acid from bioconversion of oleic acid by Pseudomonas aeruginosa

Gardner¹,

Hou

1999

J Americ Oil Chem Soc

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A previously established method was utilized to determine the stereoconfiguration of 7,10-dihydroxy-8(E )-octadecenoic acid (DHOE) from bioconversion of oleic acid by Pseudomonas aeruginosa NRRL strain B-18602 (PR3). The method involved formation of the (−)-menthoxycarbonyl (MCO) derivative of the two hydroxyls, oxidative cleavage of the double bond, and gas chromatography (GC) analysis of the two methyl-esterified diastereomeric fragments, methyl 2-MCO-decanoate and dimethyl 2-MCO-octanedioate. As described by previous workers, the 2(S)-MCO derivatives elute at earlier times by GC than the 2(R)-MCO derivatives. By comparing the GC analysis of the 2-MCO derivatives obtained from DHOE with that obtained from a partially racemized sample, DHOE was determined to be 7(S),10(S)-dihydroxy-8(E )-octadecenoic acid.

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Exciton-coupled circular dichroism (ECCD) in acyclic hydroxylated dienes: A sensitive method for the direct stereochemical assignment of lipoxygenase products

Cited by 27 publications

References 21 publications

Mollenynes B–E from the Marine Sponge Spirastrella mollis. Band-Selective Heteronuclear Single Quantum Coherence for Discrimination of Bromo–Chloro Regioisomerism in Natural Products

Mollenynes B–E from the Marine Sponge Spirastrella mollis. Band-Selective Heteronuclear Single Quantum Coherence for Discrimination of Bromo–Chloro Regioisomerism in Natural Products

The lipoxygenase gene ALOXE3 implicated in skin differentiation encodes a hydroperoxide isomerase

All (S) stereoconfiguration of 7,10‐dihydroxy‐8(E)‐octadecenoic acid from bioconversion of oleic acid by Pseudomonas aeruginosa

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