Stereochemical assignment and anti-inflammatory properties of the omega-3 lipid mediator resolvin E3

Yosuke Isobe, Makoto Arita, Ryo Iwamoto, Daisuke Urabe, Hidenori Todoroki, Koji Masuda, Masayuki Inoue, Hiroyuki Arai

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Uncontrolled inflammation is now considered to be a link between many widely occurring diseases. Thus, controlling the innate inflammatory response and its local chemical mediators has been receiving increasing attention. We recently identified a novel family of eicosapentaenoic acid (EPA)-derived mediators produced by eosinophils, denoted as resolvin E3 (RvE3), that possess potent anti-inflammatory actions both in vitro and in vivo. Carbons at 17 and 18 positions are asymmetric and thus the molecule has a total of four potential stereoisomers. Here, we assigned the stereochemistry of the conjugated double bonds and chirality of alcohols present in two natural isomers of RvE3 with four different stereoisomers prepared by total organic synthesis. The complete structures of two natural isomers of RvE3 were determined to be 17R,18S-and 17R,18R-dihydroxy-5Z,8Z,11Z,13E,15E-EPA, respectively. These natural isomers prepared by total organic synthesis displayed a potent anti-inflammatory action by limiting neutrophil infiltrations both in vitro and in vivo. The unnatural stereoisomers were much less active compared with the natural isomers, demonstrating the stereoselective action of RvE3.

Original languageEnglish
Pages (from-to)355-360
Number of pages6
JournalJournal of Biochemistry
Volume153
Issue number4
DOIs
Publication statusPublished - 2013 Apr
Externally publishedYes

Fingerprint

Isomers
Stereoisomerism
Anti-Inflammatory Agents
Lipids
Synthetic Chemistry Techniques
Eicosapentaenoic Acid
Stereochemistry
Neutrophil Infiltration
Chirality
Infiltration
Eosinophils
Carbon
Alcohols
Inflammation
Molecules
17,18-dihydroxyeicosapentaenoic acid
In Vitro Techniques

Keywords

  • 12/15-LOX
  • anti-inflammatory
  • EPA
  • resolvins
  • stereochemical assignments

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Cite this

Stereochemical assignment and anti-inflammatory properties of the omega-3 lipid mediator resolvin E3. / Isobe, Yosuke; Arita, Makoto; Iwamoto, Ryo; Urabe, Daisuke; Todoroki, Hidenori; Masuda, Koji; Inoue, Masayuki; Arai, Hiroyuki.

In: Journal of Biochemistry, Vol. 153, No. 4, 04.2013, p. 355-360.

Research output: Contribution to journalArticle

Isobe, Y, Arita, M, Iwamoto, R, Urabe, D, Todoroki, H, Masuda, K, Inoue, M & Arai, H 2013, 'Stereochemical assignment and anti-inflammatory properties of the omega-3 lipid mediator resolvin E3', Journal of Biochemistry, vol. 153, no. 4, pp. 355-360. https://doi.org/10.1093/jb/mvs151
Isobe, Yosuke ; Arita, Makoto ; Iwamoto, Ryo ; Urabe, Daisuke ; Todoroki, Hidenori ; Masuda, Koji ; Inoue, Masayuki ; Arai, Hiroyuki. / Stereochemical assignment and anti-inflammatory properties of the omega-3 lipid mediator resolvin E3. In: Journal of Biochemistry. 2013 ; Vol. 153, No. 4. pp. 355-360.
@article{07b4cb908b13434f94c98c5fefdfac71,
title = "Stereochemical assignment and anti-inflammatory properties of the omega-3 lipid mediator resolvin E3",
abstract = "Uncontrolled inflammation is now considered to be a link between many widely occurring diseases. Thus, controlling the innate inflammatory response and its local chemical mediators has been receiving increasing attention. We recently identified a novel family of eicosapentaenoic acid (EPA)-derived mediators produced by eosinophils, denoted as resolvin E3 (RvE3), that possess potent anti-inflammatory actions both in vitro and in vivo. Carbons at 17 and 18 positions are asymmetric and thus the molecule has a total of four potential stereoisomers. Here, we assigned the stereochemistry of the conjugated double bonds and chirality of alcohols present in two natural isomers of RvE3 with four different stereoisomers prepared by total organic synthesis. The complete structures of two natural isomers of RvE3 were determined to be 17R,18S-and 17R,18R-dihydroxy-5Z,8Z,11Z,13E,15E-EPA, respectively. These natural isomers prepared by total organic synthesis displayed a potent anti-inflammatory action by limiting neutrophil infiltrations both in vitro and in vivo. The unnatural stereoisomers were much less active compared with the natural isomers, demonstrating the stereoselective action of RvE3.",
keywords = "12/15-LOX, anti-inflammatory, EPA, resolvins, stereochemical assignments",
author = "Yosuke Isobe and Makoto Arita and Ryo Iwamoto and Daisuke Urabe and Hidenori Todoroki and Koji Masuda and Masayuki Inoue and Hiroyuki Arai",
year = "2013",
month = "4",
doi = "10.1093/jb/mvs151",
language = "English",
volume = "153",
pages = "355--360",
journal = "Journal of Biochemistry",
issn = "0021-924X",
publisher = "Oxford University Press",
number = "4",

}

TY - JOUR

T1 - Stereochemical assignment and anti-inflammatory properties of the omega-3 lipid mediator resolvin E3

AU - Isobe, Yosuke

AU - Arita, Makoto

AU - Iwamoto, Ryo

AU - Urabe, Daisuke

AU - Todoroki, Hidenori

AU - Masuda, Koji

AU - Inoue, Masayuki

AU - Arai, Hiroyuki

PY - 2013/4

Y1 - 2013/4

N2 - Uncontrolled inflammation is now considered to be a link between many widely occurring diseases. Thus, controlling the innate inflammatory response and its local chemical mediators has been receiving increasing attention. We recently identified a novel family of eicosapentaenoic acid (EPA)-derived mediators produced by eosinophils, denoted as resolvin E3 (RvE3), that possess potent anti-inflammatory actions both in vitro and in vivo. Carbons at 17 and 18 positions are asymmetric and thus the molecule has a total of four potential stereoisomers. Here, we assigned the stereochemistry of the conjugated double bonds and chirality of alcohols present in two natural isomers of RvE3 with four different stereoisomers prepared by total organic synthesis. The complete structures of two natural isomers of RvE3 were determined to be 17R,18S-and 17R,18R-dihydroxy-5Z,8Z,11Z,13E,15E-EPA, respectively. These natural isomers prepared by total organic synthesis displayed a potent anti-inflammatory action by limiting neutrophil infiltrations both in vitro and in vivo. The unnatural stereoisomers were much less active compared with the natural isomers, demonstrating the stereoselective action of RvE3.

AB - Uncontrolled inflammation is now considered to be a link between many widely occurring diseases. Thus, controlling the innate inflammatory response and its local chemical mediators has been receiving increasing attention. We recently identified a novel family of eicosapentaenoic acid (EPA)-derived mediators produced by eosinophils, denoted as resolvin E3 (RvE3), that possess potent anti-inflammatory actions both in vitro and in vivo. Carbons at 17 and 18 positions are asymmetric and thus the molecule has a total of four potential stereoisomers. Here, we assigned the stereochemistry of the conjugated double bonds and chirality of alcohols present in two natural isomers of RvE3 with four different stereoisomers prepared by total organic synthesis. The complete structures of two natural isomers of RvE3 were determined to be 17R,18S-and 17R,18R-dihydroxy-5Z,8Z,11Z,13E,15E-EPA, respectively. These natural isomers prepared by total organic synthesis displayed a potent anti-inflammatory action by limiting neutrophil infiltrations both in vitro and in vivo. The unnatural stereoisomers were much less active compared with the natural isomers, demonstrating the stereoselective action of RvE3.

KW - 12/15-LOX

KW - anti-inflammatory

KW - EPA

KW - resolvins

KW - stereochemical assignments

UR - http://www.scopus.com/inward/record.url?scp=84875731106&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84875731106&partnerID=8YFLogxK

U2 - 10.1093/jb/mvs151

DO - 10.1093/jb/mvs151

M3 - Article

VL - 153

SP - 355

EP - 360

JO - Journal of Biochemistry

JF - Journal of Biochemistry

SN - 0021-924X

IS - 4

ER -