Total synthesis of pro-resolving and tissue-regenerative Protectin sulfido-conjugates

Abstract

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Roles, Actions, and Therapeutic Potential of Specialized Pro-resolving Lipid Mediators for the Treatment of Inflammation in Cystic Fibrosis

“…Binding of glutathione at C16 of 17H(p)DHA produces protectin conjugated in tissue regeneration 1 (PCTR1, 16 R -glutathionyl-4 Z ,7 Z ,10 Z ,12 E ,14 E ,16 R ,17 S ,19 Z -DHA) that is converted into PCRT2 (16 R -cysteinylglycinyl-4 Z ,7 Z ,10 Z ,12 E ,14 E ,16 R ,17 S ,19 Z -DHA) and PCRT3 (16 R -cysteinyl-4 Z ,7 Z ,10 Z ,12 E ,14 E ,16 R ,17 S ,19 Z -DHA) (Rodriguez and Spur, 2015b; Ramon et al., 2016). In addition to the name giving tissue regenerative actions, PCTRs possess immune-regulatory actions on innate lymphoid cells during bacterial infection in vivo (Dalli et al., 2017).…”

Analysis of 12/15-lipoxygenase metabolism of EPA and DHA with special attention to authentication of docosatrienes

“…3 , 4 ), with the full 1 H-NMR spectra summarized in supplemental Tables S1 and S2 . These data directly establish the structures of these 15-LOX-1-derived epoxides: 14,15-LTA 5 as 14 S ,15 S - trans -epoxy-5 Z ,8 Z ,10 E ,12 E ,17 Z -EPA, and 16,17-DTA 6 as 16 S ,17 S - trans -epoxy-4 Z ,7 Z ,10 Z ,12 E ,14 E ,19 Z -DHA, with the data for the latter in accord with the synthetic epoxide ( 13 , 14 ).

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“…Notwithstanding the technical challenges, leukotriene A4 (LTA 4 ) itself has been isolated from leukocyte incubations ( 11 ), and later, we prepared LTA 4 and its 5,6- cis -epoxide analogue using recombinant 5-LOX enzyme ( 12 ). Herein, we applied the methodology using recombinant human 15-LOX-1 to preparation of the LTA-related epoxides from n -6 hydroperoxides of EPA and DHA, the latter and 22:5ω3 analogue also prepared by total chemical synthesis ( 13 , 14 , 15 , 16 ).…”

Cysteinyl maresins regulate the prophlogistic lung actions of cysteinyl leukotrienes

“…A new family of mediators in tissue regeneration, namely specialized proresolving mediator sulfido-conjugates (SPM-SCs), were recently discovered, and their stereochemical structures have been established. [10][11][12][13][14][15] These chemical mediator pathways give rise to unique bioactive structures that include maresin conjugates in tissue regeneration (MCTRs; Fig 1, A), protectin conjugates in tissue regeneration (PCTRs), and resolvin conjugates in tissue regeneration. [10][11][12]16,17 Of interest, recent results showed that MCTRs compete with LTD 4 binding on recombinant CysLT1, 18 thus warranting their investigation in mammalian tissues.…”

“…A Poroshell 120 EC-18 column (100 mm 3 4.6 mm 3 2.7 mm; Agilent Technologies, Santa Clara, Calif) was kept in a column oven maintained at 508C, and materials were eluted in a gradient of methanol/water/acetic acid from 55:45:0.01 (vol/vol/ vol) to 98:2:0.01 at 0.5 mL/min flow rate. The second system, methanol fractions from SPE containing CysLTs and SPM-SCs, was identified and profiled 11,14 Technologies) was kept in a column oven maintained at 508C, and LMs were eluted in a gradient of methanol/water/acetic acid from 55:45:0.1 (vol/vol/ vol) to 98:2:0.1 at 0.6 mL/min flow rate. Multiple reaction monitoring was used with MS/MS matching signature ion fragments for each molecule (at least 6 diagnostic ions; approximately 0.1-pg limit of detection) and standard curves (r 2 > 0.98 for each LM and pathway marker) for both systems to monitor and quantify the levels of targeted LMs.…”