An Innovative Hydrogen Peroxide-Sensing Scaffold and Insight Towards its Potential as an ROS-Activated Persulfide Donor.

Autor: Hankins RA; Department of Chemistry, Wake Forest University, Wake Downtown Campus, Winston-Salem, NC, 27101, USA., Suarez SI; Department of Chemistry, Wake Forest University, Wake Downtown Campus, Winston-Salem, NC, 27101, USA., Kalk MA; Department of Chemistry, Wake Forest University, Wake Downtown Campus, Winston-Salem, NC, 27101, USA., Green NM; Department of Chemistry, Wake Forest University, Wake Downtown Campus, Winston-Salem, NC, 27101, USA., Harty MN; Department of Chemistry, Wake Forest University, Wake Downtown Campus, Winston-Salem, NC, 27101, USA., Lukesh JC 3rd; Department of Chemistry, Wake Forest University, Wake Downtown Campus, Winston-Salem, NC, 27101, USA.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2020 Dec 01; Vol. 59 (49), pp. 22238-22245. Date of Electronic Publication: 2020 Oct 07.
DOI: 10.1002/anie.202010530
Abstrakt: Reactive sulfur species, such as hydrogen sulfide, persulfides, and polysulfides, have recently emerged as key signaling molecules and important physiological mediators within mammalian systems. To better assess the therapeutic potential of their exogenous administration, we report on the development of a unique hydrogen peroxide (H 2 O 2 )-sensing motif and its capacity for providing cellular protection against oxidative stress while serving as a reactive oxygen species (ROS)-activated persulfide donor. With the strategic implementation of a gem-dimethyl group to promote both stability and cyclization, we found the initial rate of payload release from this newly derived scaffold to be directly proportional to the concentration of H 2 O 2 and to proceed via an unprecedented pathway that avoids the production of electrophilic byproducts, a severe limitation that has plagued the physiological application of previous designs.
(© 2020 Wiley-VCH GmbH.)
Databáze: MEDLINE
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