Chiarelli, M. Paul

Emeritus Professor

Education

• 1982 B.S., Chemistry, Rockhurst College
• 1988 Ph.D., Analytical Chemistry, University of Nebraska
• 1988-1990, Postdoctoral Research Associate, University of Pittsburgh
• 1990-1994, Postdoctoral Research Associate, National Center for Toxicological Research, Jefferson, AR

Research Interests

The primary focus of our research is the use of analytical methods based on mass spectrometry for the structure determination of carcinogen-modified nucleic acids, One of the first steps in the development of some cancers is the covalent modification of DNA by a carcinogen. Molecular weight and structure determinations based on mass spectrometry can yield insight into the identity of unknown environmental carcinogens and their mechanisms of metabolism implied by specific adduct structures.  Much of our work has focused on the analysis of DNA adducts formed by the PAH Benzo[ghi]fluoranthene (B[ghi]F).  The DNA binding properties of B[ghi]F are of interest because this molecule exists in a single fixed, planar conformation.  This compound may be oxidized into syn- and anti- diol-epoxides that bind to the exocyclic nitrogens on DNA bases to yield ten different DNA adducts.   We can differentiate the structures of diastereomeric 2’-deoxynucleoside adducts and tetraols based on their tendencies to undergo water loss.  Recently we have developed a new method to sequence oligonucleotides modified by multiple arylamine carcinogens using exonuclease digestion and LC-Time-of-Flight mass spectrometry.

Publications/Research Listings

"alpha, beta-Methylene-2'-deoxynucleoside 5'-Triphosphates as Non-cleavable Substrates for DNA Polymerases: Isolation, Characterization, and Stability Studies of Novel 2'-Deoxycyclonucleosides, 3,5'-Cyclo-dG, and 2,5'-Cyclo-dT" Liang, F.; Jain, N.; Hutchens, T.; Shock, D. D.; Beard, W. A.; Wilson, S. H.; Chiarelli, M. P.; Cho, B. P.  J. Med. Chem.  2008,  51,  6460-6470.

"Sequence Verification of Oligonucleotides Containing Multiple Arylamine Modifications by Enzymatic Digestion and Liquid Chromatography Mass Spectrometry (LC/MS) "  Gao, L.; Zhang, L.; Cho, B. P. Chiarelli, M.P.;  J. Amer. Soc. Mass Spectrom.  2008, 19, 1147–1155.

"Asymmetric 1,4-disubstitution of 1,3-dienes: Palladium(II)-catalyzed formation of azido-ketones from 1,3-cyclohexadiene " El-Qisairi, A. K.; Qaseer, H. A.; Fennelly, J. P.; Chiarelli, M. P.; Henry, P. M.;  Cat. Commun.  2008,  9,  1661-1665.

"Fluorescence Probing of Aminofluorene-Induced Conformational Heterogeneity in DNA Duplexes" Jain, N.; Reshetnyak, Y. K.; Gao, L.; Chiarelli, M. P.; Cho, B. P.;  Chem. Res.  Toxicol.  2008,  21,  445-452.  

"Spectroscopic and Theoretical Insights into Sequence Effects of Aminofluorene-Induced Conformational Heterogeneity and Nucleotide Excision Repair"  Meneni, S.R.; Shell, S. M.; Gao, L.; Jurecka, P.; Wang, L.; Sponer, J.; Zou, Y.; Chiarelli, M. P.; Cho, B. P.  Biochemistry  2007,  46,  11263-11278.

"Nitramine Anion Fragmentation: A Mass Spectrometric and Ab Initio Study"  Chiarelli, M. P.; Florian, J.; MacMillan, D. K.; Gao, L.; Zhukhovskyy, V.  J. Amer. Soc. Mass Spectrom., 2007, 18,  835-841.

"Biotransformation of flumequine by the fungus Cunninghamella elegans"  Williams,  Anna .J., Deck, Joanna, Freeman, J.P.,  Chiarelli, M. P.,  Adjei,  T.M., Heinze, T.M., Sutherland, J.B.; Chemosphere, 2007, 67,  240-243.

"Improved cell typing by charge-state deconvolution of matrix-assisted laser desorption/ionization mass spectra"Wilkes, J.G.; Buzatu, D.A.;  Dare, D.J.; Dragan, D.P.; Chiarelli, M. P.;  Holland, R.D.; Beaudoin, M.; Heinze, T.M.; Nayak, R.;  Shvartsburg, A.A.; Rapid Commun.  Mass Spectrom., 2006, 20, 1595-1603.

"Acid-Base and Organic-Water Distribution Equilibria for Symetrically Substituted p,p’-Dialkyl Alkylenebisphosphonic Acids"  Zalupski, P.R.  Jensen, M. P.; Chiarizia, R.; Chiarelli, M.P.; Herlinger A. W.  Solvent Exchange and Extraction, 2006, 24, 177-195.

"Sequence effects of aminofluorene-modified DNA duplexes:thermodynamic and circular dichroism properties"  Meneni, S. R.;  D’Mello, R., Norigian, G., Baker G., Gao, L.; Chiarelli, M. P. and Cho, B.P.  Nucleic Acids Research, 2006, 34, 755-763.

"Product ion studies of Diastereomeric Benzo[ghi]fluoranthene –Deoxynucleoside Adducts by Electrospray Ionization and Quadrupole Ion Trap Mass Spectrometry"  Li, L.;  Chang, H.-F.; Chang, Olsen, K. W.;  Cho, B. P.; and Chiarelli, M. P.   Anal. Chim. Acta, 2006, 557, 191-197.

"Degradation Pathway and Generation of Monohydroxamic Acids from the Trihydroxamate Siderophore Deferrioxamine B"  Pierwola, A.; Krupinski, T.; Zalupski, P.; Chiarelli, M.P.; and Castignetti, D.   Applied and Environmental Microbiology;  2004, 70, 831-836.

"Structural Differentiation of Diastereomeric Benzo[ghi]fluoranthene Adducts by Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry and Post Source Decay" Chiarelli, M.P.; Chang, H.-F.; Olsen, K.W.; Huffer, D.M.; Barbacci, D.; and Cho, B.P. Chem. Res. Tox.  2003, 16, 1236-41.

"Differentiation of Isomeric C8-substituted Alkylaniline Adducts of Guanine by Electrospray Ionization and Tandem Quadrupole Ion Trap Mass Spectrometry"  Li, L.; Branco, P.S.; Antunes, A.M.; Marques, M.M.; Goncalves, L.L.; Beland, F.A.; Chiarelli, M.P. J. Amer. Soc. Mass Spectrom., 2003, 14, 1488-92.

"Characterization of DNA Adducts and Tetraols Derived from anti-Benzo[ghi]fluoranthene-3,4-dihydrodiol-5,5a-epoxide" Chang, H.-F.,  Huffer, D.M.; Chiarelli, M. P.;  Cho, B. P.  Chem. Res. Tox. , 2002, 15, 187-197.

"Characterization of DNA Adducts Derived from syn- Benzo[ghi]fluoranthene-3,4-dihydrodiol-5,5a-epoxide and Comparative DNA Binding Studies with Structurally-Related anti-Diolepoxides of Benzo[ghi]fluoranthene and Benzo[c]phenanthrene"  Chang, H.-F.,  Huffer, D.M.; Chiarelli, M. P.;  Blankenship, L.R.; Culp, S.J.; Cho, B. P.  Chem. Res. Tox. , 2002, 15, 198-208.