Title page for ETD etd-11142008-071704


Type of Document Dissertation
Author Gates, Arther T.
Author's Email Address agates1@lsu.edu
URN etd-11142008-071704
Title Bioanalytical Methods for Studies of Homocysteine and Novel Cardiovascular Disease Indicators
Degree Doctor of Philosophy (Ph.D.)
Department Chemistry
Advisory Committee
Advisor Name Title
Isiah M. Warner Committee Chair
Jayne C. Garno Committee Member
Kermit K. Murray Committee Member
Robert L. Cook Committee Member
Frank Tsung-Chen Tsai Dean's Representative
Keywords
  • capillary electrophoresis
  • cardiovascular disease
  • colorimetric detection
  • homocysteine
  • protein homocystamide
  • nanosensor
  • plasmon resonance
Date of Defense 2008-10-30
Availability unrestricted
Abstract
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.

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