Novel DNA Adducts- Chemical Reactions that Model the Generation of interstrand cross-links between a Guanine Residue and a 3'-alkenal end product in duplex DNA
Abstract
[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI--COLUMBIA AT REQUEST OF AUTHOR.] Modification of DNA by chemicals produced lethal biological effects such as carcinogenesis, cytotoxicity, etc. Abasic site (Ap site) can form the interstrand DNA-DNA cross-links (ICLs) with dA and dG on the opposite DNA strand. Ap site generates 3'- alkenal site in DNA by enzymatic hydrolysis. Spermine mediated strand cleavage of an Ap site in duplex DNA generates the 3'-alkenal group which forms the ICLs with adenine/guanine residue on the opposing DNA strand. But the detailed chemical structure of 3'-alkenal reaction with adenine/guanine residue was not yet established. The results here shed light on the chemical structure of ICLs generated from 3'-alkenal reaction with guanine residue. Here, we carried out the synthesis of nucleoside models that can react with dG and detailed spectroscopic structure elucidation of compound 3. Liquid chromatography-mass spectroscopy (LC-MS) helped in the determination of mass spectral properties, retention time and nuclear magnetic resonance (NMR) analysis revealed the chemical connectivity of the compound 3.
Degree
M.S.
Thesis Department
Rights
Access to files is restricted to the University of Missouri--Columbia