Summer 2006

Back Row: Jamie La, Karen Shipley, Chris McLaughlin, Alex Michaelides

Front Row: Christine Frenette, Mark Sun, Robert Paugh, Alireza Omumi and Richard Manderville

BioOrganic Chemistry

Our interest is to understand the biological consequences of DNA adduction by phenolic xenobitics that include human-made toxins, natural products and proteins with tyrosine residues. This interest stems from our findings that phenoxyl radicals, derived from the one-electron oxidation of phenols, are capable of attaching covalently to deoxyguanosine (dG) to afford C8-dG adducts. Phenoxyl radicals derived from chlorophenols may also couple to afford benzoquinone electrophiles that attach to the nitrogen atoms of the DNA bases to yield benzetheno-type adducts. Research in this area employs organic synthesis, spectroscopic techniques including NMR and molecular modeling to characterize the adducted DNAs, and molecular biology to determine whether the phenolic adducts are mutagenic. Students interested in molecular toxicology, organic and biochemistry are encouraged to read some of our recent publications and inquire about possible projects in this are of BioOrganic chemistry.

Select Publications 

• Sun, K. M.; McLaughlin, C. K.; Lantero, D. R.; Manderville, R. A. “Biomarkers for Phenol Carcinogen Exposure Act as pH-Sensing Fluorescent Probes” J. Am. Chem. Soc. 2007, 129, 1894-1895.
• Pfohl-Leszkowicz, A.; Manderville, R. A. “Ochratoxin A: An overview on toxicity and carcinogenicity in animals and humans” Mol. Nutr. Food Res. 2007, 51, 61-99.
• Tomlinson, J. T.; Park, G.; Misenheimer, J. A.; Kucera, G. L.; Hesp, K.; Manderville, R. A “Photoinduced Cytotoxicity and Thioadduct Formation by a Prodigiosin Analogue” Org. Lett. 2006, 8, 4951-4954.

· Manderville, R. A.; Pfohl-Leszkowicz, A. “Genotoxicity of Chlorophenols and Ochratoxin A” Advances in Molecular Toxicology, Fishbein, J. C. ed., 2006, 1, pp. 73-118.

· Tozlovanu, M.; Faucet-Marquis, V.; Pfohl-Leszkowicz, A.; Manderville, R. A. “Genotoxicity of the Hydroquinone Metabolite of Ochratoxin A: Structure-Activity Relationships for Covalent DNA Adduction” Chem. Res. Toxicol. 2006, 19, 1241-1247.

· McLaughlin, C. K.; Lantero, D. R.; Manderville, R. A. “Conformational Properties of a Phototautomerizable Nucleoside Biomarker for Phenolic Carcinogen Exposure” J. Phys. Chem. A 2006, 110, 6224-6230.