Advanced search options

Advanced Search Options 🞨

Browse by author name (“Author name starts with…”).

Find ETDs with:

in
/  
in
/  
in
/  
in

Written in Published in Earliest date Latest date

Sorted by

Results per page:

Sorted by: relevance · author · university · dateNew search

You searched for subject:(Mercaptopyruvate sulfurtransferase). Showing records 1 – 3 of 3 total matches.

Search Limiters

Last 2 Years | English Only

No search limiters apply to these results.

▼ Search Limiters


University of Minnesota

1. Moeller, Bryant. Characterization Of The Preclinical Cyanide Antidote Sulfanegen.

Degree: PhD, Pharmacology, 2017, University of Minnesota

Cyanide is a metabolic poison that inhibits utilization of oxygen to form ATP. The consequences of acute cyanide exposure are severe: toxic doses result in loss of consciousness, cardio and respiratory failure, hypoxic brain injury, and dose-dependent death from within minutes to hours. In a mass casualty scenario such as an industrial accident or terrorist attack, currently available cyanide antidotes would leave many victims untreated in the short time available for successful medical countermeasure administration. Therefore, there is a need for rapidly acting antidotes that can be quickly administered to large numbers of people who may be unconscious. Sulfanegen, a novel preclinical cyanide antidote, is being developed to meet this need. Sulfanegen is administered by intramuscular injection (IM), which has the advantages of requiring minimal training for first responders, as well as the potential for rapid antidotal administration to many affected people. Due to ethical issues involved with testing cyanide antidotes in human subjects, sulfanegen cannot go through the normal clinical trial path to drug approval. However, the FDA has published guidelines for evidence needed to gain approval under the “Animal Rule”, which this thesis attempts to address. The “Animal Rule” allows for new drug approval if the following conditions are met: 1) Effective in more than one animal model with a response predictive for humans, 2) Pharmacokinetics understood well enough to determine effective dose, and 3) A well-understood mechanism of action and pathology of the disease. v We first elucidated the animal models predictive for human efficacy testing by MST species comparison of the blood of many common laboratory animals. Based on this preliminary screen, species closest to that of humans were chosen to characterize the MST activities in metabolically active tissues. Using those findings, we determined swine were not an appropriate model for predicting efficacy in humans, while murine and rabbit models were appropriate. Next, we developed an isocratic UV-VIS HPLC method for characterizing the pharmacokinetics of sulfanegen in humans. Pre-column derivitization with NEM prevented the reformation of the 3-mercaptopyruvate (3MP) dimer and allowed for chromatographic detection. Moreover, this method is easily modified for applications to quality control, being able to separate sulfanegen from its precursor molecules and predicted decomposition products. Finally, we examined the potential secondary mechanisms of sulfanegen administration. MST catalyzed detoxification of cyanide to thiocyanate is the primary mechanism of action, but secondary mechanisms involving 3MP alone or in conjunction with MST contribute to the overall efficacy of sulfanegen. 3MP was found to be a potent antioxidant, capable of quenching cyanide induced ROS. Additionally, H2S generation by MST was confirmed after sulfanegen administration. Although it was confirmed that cyanohydrin formation was occurring, this probably does not contribute to reversing…

Subjects/Keywords: Antidote; Cyanide; Medical Countermeasures; Mercaptopyruvate sulfurtransferase; Sulfanegen

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Moeller, B. (2017). Characterization Of The Preclinical Cyanide Antidote Sulfanegen. (Doctoral Dissertation). University of Minnesota. Retrieved from http://hdl.handle.net/11299/206644

Chicago Manual of Style (16th Edition):

Moeller, Bryant. “Characterization Of The Preclinical Cyanide Antidote Sulfanegen.” 2017. Doctoral Dissertation, University of Minnesota. Accessed April 06, 2020. http://hdl.handle.net/11299/206644.

MLA Handbook (7th Edition):

Moeller, Bryant. “Characterization Of The Preclinical Cyanide Antidote Sulfanegen.” 2017. Web. 06 Apr 2020.

Vancouver:

Moeller B. Characterization Of The Preclinical Cyanide Antidote Sulfanegen. [Internet] [Doctoral dissertation]. University of Minnesota; 2017. [cited 2020 Apr 06]. Available from: http://hdl.handle.net/11299/206644.

Council of Science Editors:

Moeller B. Characterization Of The Preclinical Cyanide Antidote Sulfanegen. [Doctoral Dissertation]. University of Minnesota; 2017. Available from: http://hdl.handle.net/11299/206644


Virginia Tech

2. Jutabha, Promjit. Biochemical and genetic characterization of mercaptopyruvate sulfurtransferase and paralogous putative sulfurtransferases of Escherichia coli.

Degree: PhD, Biochemistry, 2001, Virginia Tech

Sulfurtransferases, including mercaptopyruvate sulfurtransferase and rhodanese, are widely distributed in living organisms. Mercaptopyruvate sulfurtransferase and rhodanese catalyze the transfer of sulfur from mercaptopyruvate and thiosulfate, respectively, to sulfur acceptors such as thiols or cyanide. There is evidence to suggest that rhodanese can mobilize sulfur from thiosulfate for in vitro formation of iron-sulfur clusters. Additionally, primary sequence analysis reveals that MoeB from some organisms, as well as ThiI of Escherichia coli, contain a C-terminal sulfurtransferase domain. MoeB is required for molybdopterin biosynthesis, whereas ThiI is necessary for biosynthesis of thiamin and 4-thiouridine in transfer ribonucleic acid. These observations led to the hypothesis that sulfurtransferases might be involved in sulfur transfer for biosynthesis of some sulfur-containing cofactors (e.g., biotin, lipoic acid, thiamin and molybdopterin). Results of a BLAST search revealed that E. coli has at least eight potential sulfurtransferases, besides ThiI. Previously, a glpE-encoded rhodanese of E. coli was characterized in our laboratory. In this dissertation, a mercaptopyruvate sulfurtransferase and corresponding gene (sseA) of E. coli were identified. In addition, the possibility that mercaptopyruvate sulfurtransferase could participate or work in concert with a cysteine desulfurase, IscS, in the biosynthesis of cofactors was examined. Cloning of the sseA gene and biochemical characterization of the corresponding protein were used to show that SseA is a mercaptopyruvate sulfurtransferase of E. coli. A strain with a chromosomal insertion mutation in sseA was constructed in order to characterize the physiological function of mercaptopyruvate sulfurtransferase. However, the lack of SseA did not result in a discernable phenotypic change. Redundancy of sulfurtransferases in E. coli may prevent the appearance of a phenotypic change due to the loss of a single sulfurtransferase. Subsequently, other paralogous genes for putative sulfurtransferases, including ynjE and yceA, were cloned. Strains with individual deletions of the chromosomal ynjE and yceA genes were also constructed. Finally, strains with multiple deficiency in potential sulfurtransferase genes, including sseA, ynjE and glpE, as well as iscS, were created. However, no phenotype associated with combinations of sseA, glpE and/or ynjE deficiency was identified. Therefore, the physiological functions of mercaptopyruvate sulfurtransferase and related sulfurtransferases remain unknown. Advisors/Committee Members: Larson, Timothy J. (committeechair), Popham, David L. (committee member), Stevens, Ann M. (committee member), Dean, Dennis R. (committee member), Chen, Jiann-Shin (committee member).

Subjects/Keywords: Mercaptopyruvate sulfurtransferase; Escherichia coli; sulfurtransferase ortholog; rhodanese

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Jutabha, P. (2001). Biochemical and genetic characterization of mercaptopyruvate sulfurtransferase and paralogous putative sulfurtransferases of Escherichia coli. (Doctoral Dissertation). Virginia Tech. Retrieved from http://hdl.handle.net/10919/28109

Chicago Manual of Style (16th Edition):

Jutabha, Promjit. “Biochemical and genetic characterization of mercaptopyruvate sulfurtransferase and paralogous putative sulfurtransferases of Escherichia coli.” 2001. Doctoral Dissertation, Virginia Tech. Accessed April 06, 2020. http://hdl.handle.net/10919/28109.

MLA Handbook (7th Edition):

Jutabha, Promjit. “Biochemical and genetic characterization of mercaptopyruvate sulfurtransferase and paralogous putative sulfurtransferases of Escherichia coli.” 2001. Web. 06 Apr 2020.

Vancouver:

Jutabha P. Biochemical and genetic characterization of mercaptopyruvate sulfurtransferase and paralogous putative sulfurtransferases of Escherichia coli. [Internet] [Doctoral dissertation]. Virginia Tech; 2001. [cited 2020 Apr 06]. Available from: http://hdl.handle.net/10919/28109.

Council of Science Editors:

Jutabha P. Biochemical and genetic characterization of mercaptopyruvate sulfurtransferase and paralogous putative sulfurtransferases of Escherichia coli. [Doctoral Dissertation]. Virginia Tech; 2001. Available from: http://hdl.handle.net/10919/28109

3. ZHAO HENG. Brain 3-Mercaptopyruvate Sulfurtransferase (3MST): Cellular Localization and Downregulation after Acute Stroke.

Degree: 2013, National University of Singapore

Subjects/Keywords: 3-Mercaptopyruvate Sulfurtransferase; Stroke; Hydrogen Sulfide; Astrocyte; Immunohistochemistry; pMCAO

Record DetailsSimilar RecordsGoogle PlusoneFacebookTwitterCiteULikeMendeleyreddit

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

HENG, Z. (2013). Brain 3-Mercaptopyruvate Sulfurtransferase (3MST): Cellular Localization and Downregulation after Acute Stroke. (Thesis). National University of Singapore. Retrieved from http://scholarbank.nus.edu.sg/handle/10635/49158

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

HENG, ZHAO. “Brain 3-Mercaptopyruvate Sulfurtransferase (3MST): Cellular Localization and Downregulation after Acute Stroke.” 2013. Thesis, National University of Singapore. Accessed April 06, 2020. http://scholarbank.nus.edu.sg/handle/10635/49158.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

HENG, ZHAO. “Brain 3-Mercaptopyruvate Sulfurtransferase (3MST): Cellular Localization and Downregulation after Acute Stroke.” 2013. Web. 06 Apr 2020.

Vancouver:

HENG Z. Brain 3-Mercaptopyruvate Sulfurtransferase (3MST): Cellular Localization and Downregulation after Acute Stroke. [Internet] [Thesis]. National University of Singapore; 2013. [cited 2020 Apr 06]. Available from: http://scholarbank.nus.edu.sg/handle/10635/49158.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

HENG Z. Brain 3-Mercaptopyruvate Sulfurtransferase (3MST): Cellular Localization and Downregulation after Acute Stroke. [Thesis]. National University of Singapore; 2013. Available from: http://scholarbank.nus.edu.sg/handle/10635/49158

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

.