Semester
Spring
Date of Graduation
2005
Document Type
Thesis
Degree Type
MS
College
School of Pharmacy
Department
Pharmaceutical Sciences
Committee Chair
Patrick Callery
Abstract
Metallothioneins (MT) are cysteine-rich intracellular proteins that sequester epoxides, such as the genotoxic styrene metabolite, styrene oxide (SO). Covalent adduct formation by the ring-opening of SO and its homologue, 1-phenylpropylene oxide (trans), with MT forms stable complexes that potentially may serve as biomarkers for epoxide exposure. MT was reacted with SO and trans-phenylpropylene oxide (PPO) separately in water. Mass spectra of adducts were obtained using electrospray ionization with positive-ion detection in an ion trap mass spectrometer. MS/MS analysis established the covalent nature of the complexation. Further experiments were conducted to determine the site of adduct formation. Molecular modeling was used to predict the most likely site of adduct formation. Alkylation and digestion were used to locate the peptide fragment where adduct formation occurred and confirm modeling results. The likeliest cysteine residue was residue 48 in the alpha domain of MT. MT-SO adducts provide a basis for the development of biomarkers.
Recommended Citation
Tarr, Sandra G., "Mass spectrometry of metallothionein adducts as candidate biomarkers of styrene oxide and 1-phenylpropylene oxide" (2005). Graduate Theses, Dissertations, and Problem Reports. 4199.
https://researchrepository.wvu.edu/etd/4199