Bioanalytical Methods for Studies of Homocysteine and Novel Cardiovascular Disease Indicators
This dissertation explores the development of analytical methods for studies of CVD biomarkers and related biomolecular indicators. Initially, spectroscopic studies were conducted to investigate the chemical reactivity of homocysteine (Hcy), an independent CVD risk factor and serological biomarker....
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ndltd-LSU-oai-etd.lsu.edu-etd-11142008-0717042013-01-07T22:52:01Z Bioanalytical Methods for Studies of Homocysteine and Novel Cardiovascular Disease Indicators Gates, Arther T. Chemistry This dissertation explores the development of analytical methods for studies of CVD biomarkers and related biomolecular indicators. Initially, spectroscopic studies were conducted to investigate the chemical reactivity of homocysteine (Hcy), an independent CVD risk factor and serological biomarker. Consequently, we proposed an alternate theory for in vivo Hcy clearance based on spontaneous pyridoxal tetrahydrothiazine (PT) formation from Hcy and pyridoxal. The validity of PT-assisted Hcy clearance was further evaluated by use of capillary electrophoretic methods, which allowed rapid monitoring of protein oligomerization in PT-protein reaction mixtures. The results of these studies suggest that PT formation is a plausible mechanism for Hcy clearance. Moreover, PT formation was shown to protect proteins from post-translational modification by homocysteine thiolactone. This dissertation also addresses the need for rapid and direct detection methods for CVD biomarkers. Accordingly, we introduced the first plasmon resonant GNP sensing scheme for protein homocystamide. The nanosensor provides visual conformation of protein homocystamide (N-Hcy-protein) by way of a red-to-blue color change. Further sensor investigations conducted with protein nanobioconjugates revealed that the GNP sensing mechanism is dependent on several complex physiochemical and biomolecular interactions including nanoparticle self-assembly, interparticle disulfide cross-linking, and modification-induced protein conformational changes. This dissertation also continues previous atherosclerotic tissue characterization studies by demonstrating the feasibility of using hybrid organic-immunoaffinity extraction for GC-MS analysis of polycyclic aromatic hydrocarbons in human heart plaque samples. This body of work is significant because it proposes new bioanalytical technologies that could enhance CVD screening and treatment. Frank Tsung-Chen Tsai Robert L. Cook Isiah M. Warner Kermit K. Murray Jayne C. Garno LSU 2008-11-21 text application/pdf http://etd.lsu.edu/docs/available/etd-11142008-071704/ http://etd.lsu.edu/docs/available/etd-11142008-071704/ en unrestricted I hereby certify that, if appropriate, I have obtained and attached herein a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to LSU or its agents the non-exclusive license to archive and make accessible, under the conditions specified below and in appropriate University policies, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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Chemistry Gates, Arther T. Bioanalytical Methods for Studies of Homocysteine and Novel Cardiovascular Disease Indicators |
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This dissertation explores the development of analytical methods for studies of CVD biomarkers and related biomolecular indicators. Initially, spectroscopic studies were conducted to investigate the chemical reactivity of homocysteine (Hcy), an independent CVD risk factor and serological biomarker. Consequently, we proposed an alternate theory for in vivo Hcy clearance based on spontaneous pyridoxal tetrahydrothiazine (PT) formation from Hcy and pyridoxal. The validity of PT-assisted Hcy clearance was further evaluated by use of capillary electrophoretic methods, which allowed rapid monitoring of protein oligomerization in PT-protein reaction mixtures. The results of these studies suggest that PT formation is a plausible mechanism for Hcy clearance. Moreover, PT formation was shown to protect proteins from post-translational modification by homocysteine thiolactone. This dissertation also addresses the need for rapid and direct detection methods for CVD biomarkers. Accordingly, we introduced the first plasmon resonant GNP sensing scheme for protein homocystamide. The nanosensor provides visual conformation of protein homocystamide (N-Hcy-protein) by way of a red-to-blue color change. Further sensor investigations conducted with protein nanobioconjugates revealed that the GNP sensing mechanism is dependent on several complex physiochemical and biomolecular interactions including nanoparticle self-assembly, interparticle disulfide cross-linking, and modification-induced protein conformational changes. This dissertation also continues previous
atherosclerotic tissue characterization studies by demonstrating the feasibility of using hybrid organic-immunoaffinity extraction for GC-MS analysis of polycyclic aromatic hydrocarbons in human heart plaque samples. This body of work is significant because it proposes new bioanalytical technologies that could enhance CVD screening and treatment. |
author2 |
Frank Tsung-Chen Tsai |
author_facet |
Frank Tsung-Chen Tsai Gates, Arther T. |
author |
Gates, Arther T. |
author_sort |
Gates, Arther T. |
title |
Bioanalytical Methods for Studies of Homocysteine and Novel Cardiovascular Disease Indicators |
title_short |
Bioanalytical Methods for Studies of Homocysteine and Novel Cardiovascular Disease Indicators |
title_full |
Bioanalytical Methods for Studies of Homocysteine and Novel Cardiovascular Disease Indicators |
title_fullStr |
Bioanalytical Methods for Studies of Homocysteine and Novel Cardiovascular Disease Indicators |
title_full_unstemmed |
Bioanalytical Methods for Studies of Homocysteine and Novel Cardiovascular Disease Indicators |
title_sort |
bioanalytical methods for studies of homocysteine and novel cardiovascular disease indicators |
publisher |
LSU |
publishDate |
2008 |
url |
http://etd.lsu.edu/docs/available/etd-11142008-071704/ |
work_keys_str_mv |
AT gatesarthert bioanalyticalmethodsforstudiesofhomocysteineandnovelcardiovasculardiseaseindicators |
_version_ |
1716477921698250752 |