Department of Medicinal Chemistry

Natalia Y. Tretyakova, Ph.D.

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    Medicinal Chemistry
  • B.S. and M.S.
    Moscow State University, 1985 – 1990
  • Ph.D.
    University of North Carolina at Chapel Hill, 1993 – 1997
  • Postdoctoral Training
    Massachusetts Institute of Technology, 1997-2000
  • Chemical Biology
  • Nucleic Acids
  • Chemical Carcinogenesis
  • Nucleoside Synthesis
  • Mass Spectrometry
  • Proteomics
  • 2-147 Cancer & Cardiovascular Research Building
  • University of Minnesota
    College of Pharmacy
    Department of Medicinal Chemistry
    2231 Sixth Street SE #2-147
    Minneapolis, MN 55455

About Natalia Y. Tretyakova, Ph.D.

The focus of our research is to investigate the structural basis for carcinogenic and anticancer activity of DNA- and protein-modifying agents. Synthetic methodologies are developed to prepare structurally modified nucleosides and amino acids representing carcinogen- and drug-induced DNA and protein adducts. The effects of nucleobase modifications on DNA structure and stability are determined by NMR spectroscopy, mass spectrometry, CD spectroscopy, and computer modeling of chemically altered DNA. Biological mass spectrometry techniques are employed to quantify the formation of DNA and protein adducts in vivo. These studies identify the molecular targets of exogenous and endogenous electrophiles and provide an insight into the origins of their biological activity. The following projects are currently underway:

Identification of DNA adducts produced by Bis-electrophiles: This research aims to identify the structures of novel DNA lesions generated by bifunctional electrophiles used in chemotherapy and generated from metabolism of xenobiotics.

Solid Phase Synthesis of DNA Oligonucleotides Containing Site- and Stereospecific DNA Adducts:
Synthetic methodologies are developed to generate DNA strands containing site- and stereospecific nucleobase lesions for structural and biological studies (e.g. NMR, mutagenesis, and polymerase bypass).

Inter-individual Differences in Metabolism of Tobacco Carcinogens: Mass spectrometry based methodologies are employed to uncover inter-individual and ethic differences in metabolism of tobacco carcinogens.

DNA Sequence Effects on Reactivity: Isotope labeling approaches are used to map the reactivity of carcinogens and drugs towards DNA nucleobases as a function of local sequence context. Unnatural DNA bases are used to establish the mechanisms of sequence-dependent reactivity.

Novel Mass Spectrometry Methodologies for Quantitative Analyses of DNA damage: we are developing novel mass spectrometry methodologies for quantitative analyzes of DNA adducts in vivo (e.g. in laboratory animals and cancer patients undergoing treatment).

Proteomics Studies of DNA-protein Cross-linking: we are employing mass spectrometry based proteomics to characterize the protein targets of bis-electrophiles that cross-link proteins to DNA.

2002 –2013 "Sequence distribution of tobacco carcinogen-DNA adducts" (NCI 5R01 CA-095039) Research Project Grant from the NIH.

2003 –2013 "DNA cross-linking by diepoxybutane" (NIH NCI 2R01-CA100670) Research Project Grant from the NIH.

2010-2014 "Mechanisms of ethnic/racial differences in lung cancer due to cigarette smoking"(1 P01 CA138338-01A1) Program Project Grant from the NIH.

Published Works

Guza, R., Simpson, P., Matter, B., Murphy, K., Jones, R., York, D., and Tretyakova, N.Y. (2011) Influence of C-5 substituted cytosine and related nucleoside analogs on the formation of benzo[a]pyrene diol- epoxide-dG adducts at CG base pairs of DNA. Nucleic Acids Research, 1-19.

Goggin, M., Sangaraju, D., Kotapati, S., Walker, V., Wickliffe, J., Swenberg, J., and Tretyakova, N.Y. (2011) Persistence and repair of bifunctional DNA adducts in laboratory mice and rats exposed to 1,3- butadiene. Chem. Res.Toxicol. 24, 809-817

Michaelson-Richie, E., Loeber, R., Fang, Q., Campbell, C., Pegg, A., and Tretyakova, N.Y. (2011) DNA- protein cross-linking by 1,2,3,4-diepoxybutane. J. Proteome Res. 9(9), 4356-4367.

Malayappan, B., Nie, B., Panchal, D., Matter, B., Johnson, L., Jacobson, P., Tretyakova, N.Y. (2010) Quantitative HPLC-ESI-MS/MS analysis of bis-N7-Guanine cross-Links in blood of cancer patients receiving cyclophosphamide therapy. Anal. Chem. 82, 3650-3658.

Seneviratne, U., Antsypovich, S., Quirk Dorr, D., Dissanayake, T., Guza, B., Thompson, C., Moser, A. and Tretyakova, N. (2010) Exocyclic deoxyadenosine adducts of 1,2,3,4-diepoxybutane:synthesis, structural characterization, and mechanistic studies. Chem. Res.Toxicol. 23(1) 118-133 (highlighted article).

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  • Last modified on August 14, 2013