Research

From G Papadantonakis

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My research interests lie in the field of experimental and computational biophysical chemistry. My investigations are focused on cancer biology. I investigate photosensors as model systems for signal transduction and protein function and I work towards understanding the mechanisms of DNA damage by environmental contaminants, reactive chemical species and photoionization.

Using ab initio quantum mechanical calculations we investigate the energetics of DNA damage. Nucleotide ionization energies provide a quantitative measurement of the electron-donating properties of DNA and RNA and they are the key initial steps than can lead to direct DNA damage and mutation. Moreover, many cancer-causing agents are electrophiles that act by attacking DNA and alkylating it. The susceptibility of nucleotides to electrophilic attack plays also a ubiquitous role in mechanisms of chemical carcinogenesis and cancer chemotherapy.

More specifically we investigate the hydration and methylation effects on the photoionization threshold energy of nucleotides and their components. We also investigate the factors influencing activation barriers for alkylation of nucleotides in aqueous solutions by carcinogenic methane diazonium ions and dimetyl sulfate through a bimolecular SN2 nucleophilic substitution mechanism.

In addition to influencing mechanisms of DNA damage induced by electrophiles and ionizing radiation, nucleotide electron donation and ionization also play a central role in mechanisms responsible for electron transport in oligonucleotides. The current goal of our current investigations is to examine sequence-specific reactivity patters of methane diazonium ions at N7 and O6 atoms of different guanines in nucleotides rich in guanine content (G runs.) This investigation will help us to understand in a more detailed manner the factors that influence barriers for reactions of methane diazonium ions and other methylating agents with DNA which eventually will result in DNA methylation. It is established that in gliomas and colorectal carcinomas, aberrant DNA methylation was detected in 40% of the tumors, whereas in non-small cell lung carcinomas, lymphomas, and head and neck carcinomas, this alteration was found in 25% of the tumors.


Selected Publications

1) A. F Philip, R. A. Nome, G. A. Papadantonakis, N. F. Scherer Wouter D. Hoff, “Spectral Tuning in Photoactive Yellow Protein by Modulation of the Shape of the Excited State Energy Surface “,” Proceedings of National Academy of Science USA,, 107, 5821-5826, (2010), DOI: 10.1073/pnas.0903092107

2) A.F. Philip, K.T. Eisenman, G. A. Papadantonakis, W. D. Hoff, “Functional Tuning of Photoactive Yellow Protein by Active Site 46,” Biochemistry, 47, 13800-13810, (2008) DOI: 10.1021/bi801730y

3) G. A. Papadantonakis, R. S. Tranter, K. Brezinsky, Y. Yang, R. B. van Breemen, P. R. LeBreton, “Low-Energy, Low-Yield Photoionization and Production of 8’-Oxo-2’-deoxyguanosine and Guanine from 2’-Deoxyguanosine,” Journal of Physical Chemistry B, 106, 7704-7712 (2002)., DOI: 10.1021/jp0206491

4) G. A. Papadantonakis, K. L. Stevenson, P. R. LeBreton, “Evidence of Temperature Dependent Activation Barriers for Near-Threshold Aqueous Photoionization of 2’-Deoxyguanosine and Tryptophan,” Chemical Physics Letters 346, 97-102, (2001). DOI: 10.1016/S0009-2614(01)00868-5

5) K. L. Stevenson, G. A. Papadantonakis, P. R. LeBreton, “Nanosecond UV Laser Photoionization of Aqueous Tryptophan: Temperature Dependence of Quantum Yield, Mechanism, and Kinetics of Hydrated Electron Decay,” Journal of Photochemistry and Photobiology A: Chemistry 133(3), 159-167, (2000), DOI: 10.1016/S1010-6030(00)00235-5

6) H. Fernando, G. A. Papadantonakis, N.S. Kim, Pierre R. LeBreton,” Conduction-Band-Edge Ionization Thresholds for DNA Components In Aqueous Solutions,” Proceedings of National Academy of Science USA, 95, 5550-5555, (1998). DOI: 10.1073/pnas.95.10.5550

7) H. Fernando, G. A. Papadantonakis, N.S. Kim, Pierre R. LeBreton, , In Molecular Modeling of Nucleic Acids; ACS Symposium Series 682; Leontis N., SantaLucia J., Jr., Eds.; American Chemical Society, Washington, D.C., 1998; p.p. 18-40.

Posters

1) Daniel R. Eichler, Haley A. Hamann, Katherine A. Harte and George A. Papadantonakis, “Effects of Hydration and Methylation on the Photoionization Threshold Energy of DNA Components and on the Activation Barriers for Guanine Methylation by Dimethyl Sulfate”. 60th Annual Biophysical Society Meeting, February 27- March 2, 2016, Los Angeles, CA.

2) Daniel R. Eichler, Haley A. Hamann, Katherine A. Harte and George A. Papadantonakis, “Activation Barriers for Alkylation of Nucleotides in Aqueous Solutions by Dimethyl Sulfate, Diethyl Sulfate and Related Compounds”. 251st American Chemical Society National Meeting and Exhibition, March 13-17, 2016, San Diego, CA.

3) Allison M. Tambeaux, Jie Ren, George A. Papadantonakis,“Towards Understanding the Methylation Effect on the Aqueous Photoionization Energy of DNA Components”, 56th Biophysical Society Annual Meeting, February 25-29, 2012, San Diego, CA.

CAPSTONES and LASURI Presentstions (Honors College)

1) Anam Chhatriwala and George A. Papadantonakis, “When Good Cells Go Bad: the Role of p53”. In UIC Research Forum LASURI and CAPSTONES (Honors College), Spring 2015

2) Haneul Yang and George A. Papadantonakis, “Effect of Hydration on the Ionization Potential of Nucleotides”. In UIC Research Forum LASURI, Spring 2014

3) Kenneth Chow and George A. Papadantonakis, “Comparison of Phylogenetic Trees Based on Taxonomy and Amino Acid Sequences of Phosphoglycerate Kinase Proteins”. In UIC Research Forum CAPSTONES (Honors College), Spring 2012

4) Ruchi D. Patel, Wouter D. Hoff, George A. Papadantonakis, “Probing the Folding Mechanism of Photoactive Yellow Protein”. In UIC Research Forum CAPSTONES (Honors College), Spring 2012

5) Luis Manon, Jie Ren, George A. Papadantonakis, “Photoionization Threshold Energy of DNA Components” .In UIC Research Forum – CAPSTONES (Honors College), Spring 2012

6) Hina Menk, Matthew Pearce, Miguel Del Toral, Paige Taylor, George A. Papadantonakis, “ Phylogenetic Analysis and Sequence Specific Alignment of p53 Target Genes”. In UIC Research Forum CAPSTONES (Honors College), Spring 2012

7) Penelope Burikas, Joanna Park. George A. Papadantonakis, “Comparison of Phylogenetic Trees Based on Taxonomy and Amino Acid Sequence of Photoactive Yellow Protein”. In UIC Research Forum CAPSTONES (Honors College), Spring 2012

8) Jenna Bosnos, Hakim Ogutcu, George A. Papadantonakis, “Sequencing the Human Genome: NIH or another Way? Comparison of the Hierarchical Shotgun Sequence with Whole Genome Shotgun Sequence” In UIC Research Forum CAPSTONES (Honors College), Fall 2011

9) Noa Krugliak, Jie Ren, George A. Papadantonakis, “The Energetics of Nucleotide Ionization in Water-Counterion Environments”. CAPSTONES (Honors College), Spring 2010

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