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Development of novel controllable hydrogen sulfide donors

Posted on:2015-07-13Degree:Ph.DType:Dissertation
University:Washington State UniversityCandidate:Zhao, YuFull Text:PDF
GTID:1474390017989191Subject:Chemistry
Abstract/Summary:
Hydrogen sulfide (H2S) is as an important cell signaling molecule. It has been recognized as a mediator of many physiological and/or pathological processes. The production of H2S in mammalian systems has been attributed to three enzymes: cystathionine beta-synthase (CBS), cystathionine gamma-lyase (CSE), and 3-mercaptopyruvate sulfur-transferase (MPST). Although H2S's exact chemical and biochemical modes of action are still not fully understood, the production of endogenous H 2S and exogenously administration of H2S have been demonstrated to exert protective effects in many pathologies. In this field, H2S-releasing agents (or donors) are important research tools for the study of H2S biological functions. However, currently available H2S donors are very limited and H2S generations from these compounds are too fast and uncontrollable. Rapid release of H2S may cause acute changes in blood pressure. Ideal H2S donors, from therapeutic point of view and for the applications in H2S-related biological research, should release H2S slowly in moderate amounts.;To this end, we have developed new controllable H2S donors, such as N-mercapto-based donors and perthiol-based donors. These molecules were stable in aqueous solutions. However, in the presence of cellular thiols (i.e. cysteine and glutathione), time-dependent H2S release was observed. In addition, protective effects of these donors in living systems were also observed. These findings suggest that both N-mercapto-based and perthiol-based molecules are potent H2S donors and they have potential therapeutic benefits due to H2S release.
Keywords/Search Tags:H2S, Donors, Release
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