Alleviating Cellular Oxidative Stress through Treatment with Superoxide-Triggered Persulfide Prodrugs.

Autor: Wang Y; Department of of Chemistry, Virginia Tech Center for Drug Discovery, Macromolecules Innovation Institute, Virginia Tech, Blacksburg, VA, 24061, USA., Dillon KM; Department of of Chemistry, Virginia Tech Center for Drug Discovery, Macromolecules Innovation Institute, Virginia Tech, Blacksburg, VA, 24061, USA., Li Z; Department of of Chemistry, Virginia Tech Center for Drug Discovery, Macromolecules Innovation Institute, Virginia Tech, Blacksburg, VA, 24061, USA., Winckler EW; Department of of Chemistry, Virginia Tech Center for Drug Discovery, Macromolecules Innovation Institute, Virginia Tech, Blacksburg, VA, 24061, USA., Matson JB; Department of of Chemistry, Virginia Tech Center for Drug Discovery, Macromolecules Innovation Institute, Virginia Tech, Blacksburg, VA, 24061, USA.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2020 Sep 14; Vol. 59 (38), pp. 16698-16704. Date of Electronic Publication: 2020 Jul 23.
DOI: 10.1002/anie.202006656
Abstrakt: Overproduction of superoxide anion (O 2 .- ), the primary cellular reactive oxygen species (ROS), is implicated in various human diseases. To reduce cellular oxidative stress caused by overproduction of superoxide, we developed a compound that reacts with O 2 .- to release a persulfide (RSSH), a type of reactive sulfur species related to the gasotransmitter hydrogen sulfide (H 2 S). Termed SOPD-NAC, this persulfide donor reacts specifically with O 2 .- , decomposing to generate N-acetyl cysteine (NAC) persulfide. To enhance persulfide delivery to cells, we conjugated the SOPD motif to a short, self-assembling peptide (Bz-CFFE-NH 2 ) to make a superoxide-responsive, persulfide-donating peptide (SOPD-Pep). Both SOPD-NAC and SOPD-Pep delivered persulfides/H 2 S to H9C2 cardiomyocytes and lowered ROS levels as confirmed by quantitative in vitro fluorescence imaging studies. Additional in vitro studies on RAW 264.7 macrophages showed that SOPD-Pep mitigated toxicity induced by phorbol 12-myristate 13-acetate (PMA) more effectively than SOPD-NAC and several control compounds, including common H 2 S donors.
(© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Databáze: MEDLINE
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