W. David Wilson

Regents Professor, Biophysical Chemistry
Ph.D., Purdue University, (1970)

Dr. Dave Wilson
Department of Chemistry
Georgia State University
University Plaza
Atlanta, Georgia 30303-3083
Phone: (404) 651-3903
Fax: (404) 651-1416
Office: 540 Natural Science Center
chewdw@panther.gsu.edu

Research Interests

A number of collaborative projects are underway and all of them focus on the structure and interaction properties of nucleic acids. We are investigating and developing a range of compounds that interact with different sequences and structures of DNA. We are particularly interested in the design drugs that can inhibit specific organisms by forming complexes in the DNA minor groove at unique sequences. A range of solution and molecular modeling experiments are being conducted on minor groove complexes of compounds that interact with DNA oligomer sequences that mimic selected sequences from the organism to be targeted. These studies lead to a molecular model of the complex as a computer model, and logical variations of the drug structure to enhance the DNA interactions can be proposed and initially tested in the computer. We are particularly interested in developing new classes of agents that can interact with DNA as cooperative dimers. Such compounds have the ability to simultaneously recognize both strands of DNA to significantly enhance interaction strength and specificity. We are establishing rules for the specific interaction of heterocyclic dimers with DNA and we now have new types compounds that can recognize a number of DNA sequences with high specificity.

2,5-bis-(4-amidinophenyl)furan bound in the minor groove of DNA We are also involved in a number of collaborative efforts to identify and characterize compounds that can bind to the DNA quadruplex that forms from the telomere sequence at the ends of human chromosomes. Compounds that bind to the quadruplex have the ability to inhibit the telomerase enzyme that extends the telomere to maintain the viability of rapidly dividing cells. Since many human cancers require telomerase activity, inhibition of this enzyme is a very attractive method to selectively attack cancer cells. A number of very promising compounds have been discovered and are under study. At the same time, we are searching for general principles that can be used in the design of quadruplex/telomere targeting compounds.

Our laboratory and the Chemistry Department have excellent equipment and facilities for studies of nucleic acids and their complexes. We have a BIAcore biosensor-surface plasmon resonance instrument, spectroscopy equipment, calorimeters that include isothermal titration and differential scanning instruments, and outstanding array of NMR spectrometers.

All of these projects involve essential collaborations with other scientists at Georgia State University, at other institutes and universities, and in industry.

The image to the right shows 2,5-bis-(4-amidinophenyl)furan bound in the minor groove of DNA. The binding site is composed of the sequence 5'AATT3' (the adenines are magenta, the thymines are orange). DNA minor groove binding compounds, such as this one, are prime candidates for new drugs.

Recent Publications from the Wilson Laboratory:

"Design and Analysis of Molecular Motifs for Specific Recognition of RNA." Ke Li, M. Fernandez-Saiz, C. T. Rigl, Arvind Kumar, K. Ragunathan, A. W. McConnaughie, David W. Boykin, H.-J. Schneider, W. David Wilson, Bioorg. Med. Chem., 5, 1157 (1997).

"Structural RNA Mimics:N3'-P5' Phosphoramidate Analogs of HIV-1 RRE and TAR RNA Form A-Type Helicies That Bind Specifically to Rev and Tat Related Peptides." C. T. Rigl, D. Lloyd, D. S. Tsou, S. Gryaznov and W. D. Wilson, Biochemistry, 36, 650 (1997).

"Cytotoxicity of Bis(phenylamidinium)furan Alkyl Derivatives in Human Tumor Cell Lines: Relation to DNA Minor Groove Binding." S. Neidle, L. R. Kelland, J. O. Trent, I. J. Simpson, D. W. Boykin, A. Kumar, and W. D. Wilson, Bioorg. Med. Chem. Lett., 7, 1403 (1997).

"Modulation of the Rev-RRE Interaction by Aromatic Heterocyclic Compounds." Maria Zapp, D. W. Young, Arvind Kumar, R. Singh, David W. Boykin, W. David Wilson, and M. R. Green, Bioorg. Med. Chem., 5, 1149 (1997).

"Anti-Pneumocystis carinii Pneumonia Activity of Dicationic Carbazoles." D. A. Patrick, D. W. Boykin, W. D. Wilson, F. A. Tanious, J. Spychala, B. C. Bender, J. E. Hall, C. C. Dykstra, K. A. Ohemeng and R. R. Tidwell, Eur. J. Med. Chem., 32, 965 (1997).

"A New Type of DNA Minor-Groove Complex: Carbazole Dication-DNA Interactions." Farial. A. Tanious, Daoyuan Ding, Donald A. Patrick, Richard R. Tidwell and W. David Wilson, Biochemistry, 36, 15315 (1997).

"Evaluation of Drug-Nucleic Acid Interactions by Thermal Melting Curves." W. David Wilson, F. A. Tanious, M. Fernandez-Saiz, and C. T. Rigl, in Methods in Mol. Biol.: Drug-DNA Interaction Protocols (K. Fox, Ed.), 90, 219 (1997).

"Analysis of the Structure and Folding of the 3' Genomic RNA of Flaviviruses." P. Shi, T. Sklyarevskaya, P. Kebbekus, M. Brinton, and W. D. Wilson, Nucleic Acid Symp. Ser., 36, 52 (1997).

"Anti-Pneumocystis carinii Pneumonia Activity of Dicationic Diaryl Methylpyrimidines." D. W. Boykin, A. Kumar, M. Bajic, G. Xiao, W. D. Wilson, B. C. Bender, D. McCurdy, J. E. Hall, and R. R. Tidwell, Eur. J. Med. Chem., 32, 965 (1997).

"NMR Solution Structure of of the N3'-P5' Phosphoramidate Duplex d(CGCGAATTCGCG)2 by the Iterative Relaxation Matrix Approach." Daoyuan Ding, Sergei Gryaznov, and W. David Wilson, Biochemistry , 37, 12082 (1998).

"Design and Analysis of Organic Cations That Inhibit Interactions of the HIV-1 Rev Protein with RRE RNA." Ke Li, Ge Xiao, Ted Rigl, Arvind Kumar, David W. Boykin and W. David Wilson, in Structure, Motion, Interaction and Expression of Biological Macromolecules, Vol. II (R. H. Sarma and M. H. Sarma, Eds.), Adenine Press, 137 (1998).

"Extended Aromatic Furan Amidino Derivatives as Anti-Pneumocystis carinii Agents." K. Hopkins, W. D. Wilson, B. C. Bender, D. McCurdy, J. E. Hall, and R. R. Tidwell, M. Bajic, A. Kumar, D. W. Boykin, J. Med. Chem., 41, 3872 (1998).

"Strategies For Inhibition Of RNA-Protein Complexes: From Small Molecules To Nucleic Acid Decoys." W. David Wilson, Ge Xiao, Ke Li, Arvind Kumar, David W. Boykin, Daoyuan Ding, Ted Rigl, Muthiah Manoharan and Sergei Gryaznov, Nucleic Acids Research Symposium Series, 39, 135 (1998).

"2,5-Bis[4-(N-alkylamidino)phenyl]furans as Anti-Pneumocystis carinii Agents." D. W. Boykin, A. Kumar, G. Xiao, W. D. Wilson, B. C. Bender, D. McCurdy, J. E. Hall, and R. R. Tidwell, J. Med. Chem., 41, 124 (1998).

"Nucleic Acid Interactions of Unfused Aromatic Cations: Evaluation of Proposed Minor-Groove, Major-Groove and Intercalation Binding Modes." W. David Wilson, Farial A. Tanious, Daoyuan Ding, Arvind Kumar, David W. Boykin, P. Colson, C. Houssier, Christian Bailly, J. Am. Chem. Soc., 120, 10310 (1998).

"Electrochemically Active Threading Intercalator with High Double Stranded DNA Selectivity." S. Takenaka, Y. Uto, H. Saita, M. Yokoyama, H. Kondo and W. D. Wilson,Chem. Comm., 1111 (1998).

"DNA and RNA Intercalators." W. David Wilson in DNA and Aspects of Molecular Biology (E. Kool, Ed.) Volume 7 in the Series Comprehensive Natural Products Chemistry (D. Barton and K. Nakanishi, Eds.), Chapt. 8 (1999).

"Inhibition of HIV-1 Tat-TAR Interaction by Diphenylfuran Derivatives: Effects of the Terminal Basic Side Chains." N. Gelus, C. Bailly, F. Hamy, T. Klimkait, W. David Wilson and David W. Boykin, Bioorganic and Medicinal Chemistry, 7, 1089 (1999).

"Relationships Between Topoisomerase II Inhibition, Sequence-Specificity and DNA Binding Mode of Dicationic Diphenylfuran Derivatives." Christian Bailly, L. Dassonneville, C. Carrasco, D. Lucas, Arvind Kumar, David W. Boykin and W. David Wilson, AntiCancer Drug Design, 14, 47 (1999).

"Dicationic Dibenzofuran Derivatives as Anti-Pneumocystis Carinii Pneumonia Agents: Synthesis, DNA Binding Affinity, and Anti-PCP Activity." Wang, S. H. Hall, J. E., Tanious, F. A., Wilson, W. D., Patrick, D. A., McCurdy, D. R., Bender, B. C. and Tidwell, R. R. European J. Med. Chem., 34, 215 (1999).

"2,4-Diphenyl Furan Diamidines as Novel Anti-Pneumocystis carinii Pneumonia Agents." I. Francesconi, W. D. Wilson, F. A. Tanious, J. E. Hall, B. C. Bender, R. R. Tidwell, D. McCurdy and D. W. Boykin, J. Med. Chem., 42, 2260 (1999).

"Selective Photocleavage of DNA and RNA by Anthraquinone Derivatives: Targeting the Single-Strand Region of Hairpin Structures." Maria Fernandez-Saiz, Paul T. Henderson, W. David Wilson, Gary B. Schuster, Photochem. Photobiol., 70, 847 (1999).

"Synthesis and anti-Pneumocystis carinii Pneumonia Activity Of Novel Dicationic Dibenzothiophenes And Orally Active Prodrugs." Donald A. Patrick, James Edwin Hall, B. C. Bender, D. R. McCurdy, W. David Wilson, Farial A. Tanious, S. Saha and Richard R. Tidwell, European Journal of Medicinal Chemistry, 34, 575 (1999).

"Calorimetric studies on the pH dependence in hairpin formation within the human enkephalin enhancer region." H. P. Hopkins, D. D. Hamilton, W. D. Wilson, C. T. McMurray, Journal of Solution Chemistry, 28, 759-768 (1999).

"Large Hydrophobic Contributions Are Involved in DNA Minor-Groove Complex Formation with a Series of Diphenylfuran Dications: Surface Plasmon Resonance and Isothermal Titration Calorimetry Studies." Suzann Mazur, Farial Tanious, Daoyuan Ding, Arvind Kumar, David W. Boykin, Stephen Neidle and W. David Wilson, J. Mol. Biol., 300, 321(2000).

"Determination of the Refractive Index Increments of Small Molecules for Correction of Surface Plasmon Resonance Data." Tina M. Davis and W. David Wilson, Anal. Biochem., 284, 348 (2000).

"Effects of Compound Structure on Carbazole Dication-DNA Complexes: Tests of the Minor-Groove Complex Models." Farial A. Tanious, Daoyuan Ding, Donald A. Patrick, Christian Bailly, Richard R. Tidwell, and W. David Wilson, Biochemistry, 39, 12091 (2000).

"The Flexible Structure of DNA: Ion Dependence of Minor-Groove Structure and Dynamics." Donald Hamelberg, Lori McFail-Isom, Loren Dean Williams and W. David Wilson, J. Am. Chem. Soc., 122, 10513 (2000).

"Amplification of Pepleomycin-Mediated DNA Cleavage and Apoptosis by Unfused Aromatic Cations." Shosuke Kawanishi, Shinji Oikawa, Michiko Kawanishi, Hiroshi Sugiyama, Isao Saito, Lucjan Strekowski, and W. David Wilson, Biochemistry, 39, 13210 (2000).

"Diguanidino and Reversed Diamidino 2,5-Diarylfurans as Antimicrobial Agents." Chad E. Stephens, Farial Tanious, Susan Kim, W. David Wilson, W. A. Schell, J. R. Perfect, S. C. Franzblau and David W. Boykin, J. Med. Chem., 44, 1741 (2001).

"Novel Dications With Unfused Aromatic Systems: Trithiophene And Trifuran Derivatives Of Furimidazoline." Petr Bilik, Farial Tanious, Arvind Kumar,W. David Wilson, David W. Boykin, Pierre Colson, Claude Houssier, Michael Facompré, Christelle Tardy, and Christian Bailly, CHEMBIOCHEM, 2, 559 (2001).

"Evaluation of the Influence of Compound Structure on Stacked-Dimer Formation in the DNA Minor Groove." Lei Wang, Carolina Carrasco, Arvind Kumar, Chad E. Stephens, Christian Bailly, David W. Boykin, and W. David Wilson, Biochemistry, 40, 2511, (2001).

"Inhibition of the HIV-1 Rev-RRE Complex Formation by Unfused Aromatic Cations." Ge Xiao, Arvind Kumar, Ke Li, C. Ted Rigl, Miroslav Bajic, Tina Davis, David W. Boykin and W. David Wilson, Bioorg. Med. Chem., 9, 1097 (2001).

"A Heterocyclic Inhibitor of the Rev-RRE Complex Binds to RRE as a Dimer." Ke Li, Tina Davis, Christian Bailly, Arvind Kumar, David W. Boykin and W. David Wilson, Biochemistry, 40, 1150 (2001).

"Sequence-Dependent Binding of Bis-amidine Carbazole Dications to DNA." F. A. Tanious, W. David Wilson, D. A. Patrick, R. R. Tidwell, P. Colson, C. Houssier, C. Tardy, C. Bailly, Eur. J Biochem., 268, 3455 (2001).

"BIAcore and DNA Footprinting for Discovery and Development of New DNA Targeted Therapeutics and Reagents." W. David Wilson, Lei Wang, Farial Tanious, Arvind Kumar, David W. Boykin, Carolina Carrasco, and Christian Bailly, BIAcore Journal, 1, 15 (2001).

"Recognition of ATGA Sequences by the Unfused Aromatic Dication DB293 Forming Stacked Dimers in the DNA Minor Groove." Bailly C., Tardy C., Wang L., Armitage B., Hopkins K., Kumar A., Schuster G. B., Boykin D. W., Wilson W. D., Biochemistry, 40, 9770 (2001).

"Influence of the Dynamic Positions of Cations on the Structure of the DNA Minor Groove: Sequence-Dependent Effects." Donald Hamelberg, Loren Dean Williams, and W. David Wilson, J. Am. Chem. Soc., 123, 7745 (2001).

"Surface Plasmon Resonance Biosensor Analysis of RNA-Small Molecule Interactions." Tina M. Davis and W. David Wilson, Methods in Enzymology, 340, 22 (2001).

"Structure, Analysis and DNA Binding Properties of the Indolocarbazole Antitumor Drug NB-506." Carolina Carrasco, Hervé Vezin, W. David Wilson, Jinsong Ren and Jonathan B. Chaires and Christian Bailly, Anticancer Drug Design, 16, 99 (2002).

"Substituent Changes Strongly Influence Sequence Specific DNA Recognition by Symmetric Bis-benzimidazoles." Christian Bailly, Carolina Carrasco, Stephen Neidle and W. David Wilson, Nucleic Acids Research, submitted, (2002).

"Recognition of T-G Mismatched Base Pairs in DNA by Stacked Imidazole-Containing Polyamides: Surface Plasmon Resonance and Circular Dichroism Studies." Eilyn R. Lacy, Kari K. Cox, W. David Wilson and Moses Lee, Nucleic Acids Research, 30, 1834(2002).

"Influence of an N-Terminal Formamido Group on the Sequence Recognition of DNA by Polyamides." Eilyn R. Lacy, N. Minh Le, Carly A. Price, Moses Lee and W. David Wilson, J. Am. Chem. Soc., 124, 2153(2002).

"Comparative Thermodynamics for Monomer and Dimer Sequence-Dependent Binding of a Heterocyclic Dication in the DNA Minor Groove." Lei Wang, Arvind Kumar, David W. Boykin, Christian Bailly and W. David Wilson, J. Mol. Biol., 317, 361 (2002).

"Distribution of Furamidine Analogues in Tumor Cells: Influence of the Number of Positive Charges." A. Lansiaux, L. Dassonnville, M. Facompre, A. Kumar, C. E. Stephens, M. Bajic, F. Tanious, W. D. Wilson, D. W. Boykin, and C. Bailly, J. Med. Chem. 1994 (2002).

"Studies on the Unique RNA Duplex Destabilization by an Azoniacyclophane: NMR Titrations with Mono- and Oligonucleotides of the RNA and DNA Types." M. Fernandez-Saiz, F. Werner, T. M. Davis, Hans-Jörg Schneider, and W. David Wilson, Eur. J. Org. Chem., in press (2002).

"DNA Sequence Recognition by the Indolocarbazole Antitumor Antibiotic AT2433-B1 and Its Diastereomer." C. Carrasco, M. Facompre, J. D. Chisholm, D. van Vranken, W. D. Wilson and C. Bailly, Nucleic Acids Research, 30, 1774 (2002).

"Affinities and Rates on a Chip: SPR Analysis of Biomolecular Interactions." W. David Wilson, Science, 295, 2103 (2002).

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