Redox properties and human serum albumin binding of nitro-oleic acid

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F19%3A00509880" target="_blank" >RIV/68081707:_____/19:00509880 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/61989592:15110/19:73595256 RIV/60076658:12310/19:43899433

Výsledek na webu

<a href="https://doi.org/10.1016/j.redox.2019.101213" target="_blank" >https://doi.org/10.1016/j.redox.2019.101213</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.redox.2019.101213" target="_blank" >10.1016/j.redox.2019.101213</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Redox properties and human serum albumin binding of nitro-oleic acid

Popis výsledku v původním jazyce

Nitro-fatty acids modulate inflammatory and metabolic stress responses, thus displaying potential as new drug candidates. Herein, we evaluate the redox behavior of nitro-oleic acid (NO2-OA) and its ability to bind to the fatty acid transporter human serum albumin (HSA). The nitro group of NO2-OA underwent electrochemical reduction at 0.75 V at pH 7.4 in an aqueous milieu. Based on observations of the R-NO2 reduction process, the stability and reactivity of NO2-OA was measured in comparison to oleic acid (OA) as the negative control. These electrochemically-based results were reinforced by computational quantum mechanical modeling. DFT calculations indicated that both the C9-NO2 and C10-NO2 positional isomers of NO2-OA occurred in two conformers with different internal angles (69 degrees and 110 degrees) between the methyl- and carboxylate termini. Both NO2-OA positional isomers have LUMO energies of around 0.7 eV, affirming the electrophilic properties of fatty acid nitroalkenes. In addition, the binding of NO2-OA and OA with HSA revealed a molar ratio of similar to 7:1 [NO2-OA]: [HSA]. These binding experiments were performed using both an electrocatalytic approach and electron paramagnetic resonance (EPR) spectroscopy using 16-doxyl stearic acid. Using a Fe(DTCS)(2) spin-trap, EPR studies also showed that the release of the nitro moiety of NO2OA resulted in the formation of nitric oxide radical. Finally, the interaction of NO2-OA with HSA was monitored via Tyr and Trp residue electro-oxidation. The results indicate that not only non-covalent binding but also NO2-OA-HSA adduction mechanisms should be taken into consideration. This study of the redox properties of NO2-OA is applicable to the characterization of other electrophilic mediators of biological and pharmacological relevance.

Název v anglickém jazyce

Redox properties and human serum albumin binding of nitro-oleic acid

Popis výsledku anglicky

Nitro-fatty acids modulate inflammatory and metabolic stress responses, thus displaying potential as new drug candidates. Herein, we evaluate the redox behavior of nitro-oleic acid (NO2-OA) and its ability to bind to the fatty acid transporter human serum albumin (HSA). The nitro group of NO2-OA underwent electrochemical reduction at 0.75 V at pH 7.4 in an aqueous milieu. Based on observations of the R-NO2 reduction process, the stability and reactivity of NO2-OA was measured in comparison to oleic acid (OA) as the negative control. These electrochemically-based results were reinforced by computational quantum mechanical modeling. DFT calculations indicated that both the C9-NO2 and C10-NO2 positional isomers of NO2-OA occurred in two conformers with different internal angles (69 degrees and 110 degrees) between the methyl- and carboxylate termini. Both NO2-OA positional isomers have LUMO energies of around 0.7 eV, affirming the electrophilic properties of fatty acid nitroalkenes. In addition, the binding of NO2-OA and OA with HSA revealed a molar ratio of similar to 7:1 [NO2-OA]: [HSA]. These binding experiments were performed using both an electrocatalytic approach and electron paramagnetic resonance (EPR) spectroscopy using 16-doxyl stearic acid. Using a Fe(DTCS)(2) spin-trap, EPR studies also showed that the release of the nitro moiety of NO2OA resulted in the formation of nitric oxide radical. Finally, the interaction of NO2-OA with HSA was monitored via Tyr and Trp residue electro-oxidation. The results indicate that not only non-covalent binding but also NO2-OA-HSA adduction mechanisms should be taken into consideration. This study of the redox properties of NO2-OA is applicable to the characterization of other electrophilic mediators of biological and pharmacological relevance.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Redox Biology

ISSN

2213-2317

e-ISSN

—

Svazek periodika

24

Číslo periodika v rámci svazku

JUN 2019

Stát vydavatele periodika

NL - Nizozemsko

Počet stran výsledku

12

Strana od-do

101213

Kód UT WoS článku

000471255400042

EID výsledku v databázi Scopus

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