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W. David Wilson Professor, Biophysical Chemistry Ph.D., Purdue University, (1970) Dr. W. Wilson Department of Chemistry Georgia State University P.O. Box 4098 Atlanta, Georgia 30302-4098
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Research Interests
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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.
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.
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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.Recent Publications from the Wilson Laboratory:
"Molecular Determinants For DNA Minor Groove Recognition: Design Of A Bis-Guanidinium Derivative Of Ethidium That Is Highly Selective For AT-Rich DNA Sequences." Christian Bailly, Reem K. Arafa, Farial A. Tanious, William Laine, Christèle Tardy, Amélie Lansiaux, Pierre Colson, David W. Boykin and W. David Wilson, Biochemistry, 44, 1941 (2005).
"Extending The Language Of DNA Molecular Recognition By Polyamides: Unexpected Influence Of Imidazole And Pyrrole Arrangement On Binding Affinity And Specificity." Karen L. Buchmueller, A. Staples, C. Howard, S. Horick, P. Uthe, N. Le, K. Cox, Binh Nguyen, K. Pacheco, W. David Wilson and Moses Lee, J. Am. Chem. Soc., 127, 742 (2005).
"Triple-Helix DNA Selective 2-(2-Naphthyl)Quinoline Intercalators." L. Strekowski, A. N. Parker, M. Hojjat, M. Say, O. Zegrocka-Stendel, S. E. Patterson, Farial A. Tanious and W. David Wilson, Acta Pol. Pharm., 61, 70 (2005).
"Chiral Discrimination In Binding Of Enantiomers Of 2-(Aminoalkoxy)-Substituted 4-(2-Thienyl)Pyrimidines And 4,6-Bis(2-Thienyl)Pyrimidines With Duplex DNA". L. Strekowski, M. T. Cegla, V. Honkan, H. Buczak, W. R. Winkeljohn, A. L. Baumstark, W. David Wilson, Bioorg. Med. Chem. Lett., 15, 2720 (2005).
"Telomestatin And Diseleno Sapphyrin Bind Selectively To Two Different Forms Of The Human Telomeric G-Quadruplex Structure." E. M. Rezler, J. Seenisamy, S. Bashyam, M. Y. Kim, E. White, W. David Wilson and Laurence H. Hurley, J. Am. Chem. Soc., 127, 9439 (2005).
"Binding-Linked Protonation Of A DNA Minor Groove Agent." Binh Nguyen, J. Stanek and W. David Wilson, Biophys J., 90, 1319 (2006).
"3D QSAR On A Library Of Heterocyclic Diamidine Derivatives With Antiparasitic Activity." P. Athri, T. Wenzler, P. Ruiz, Reto Brun, David W. Boykin, Richard Tidwell and W. David Wilson, Bioorg. Med. Chem., 14, 3144 (2006).
"DNA Binding Affinity Of Bisguanidine And Bis(2-Aminoimidazoline) Derivatives With In Vivo Antitrypanosomal Activity." Christophe Dardonville, Michael P. Barrett, Reto Brun, M. Kaiser, F. Tanious and W. David Wilson, J. Med. Chem., 49, 3748 (2006).
"Trisubstituted Acridines As G-Quadruplex Telomere Targeting Agents. Effects Of Extensions Of The 3,6- And 9-Side Chains On Quadruplex Binding, Telomerase Activity, And Cell Proliferation." M. J. Moore, C. M. Schultes, J. Cuesta, F. Cuenca, M. Gunaratnam, Farial A. Tanious, W. David Wilson and Stephen Neidle, J. Med. Chem., 49, 582 (2006).
"Binding Of Netropsin And 4,6-Diamidino-2-Phenylindole To An A2T2 DNA Hairpin: A Comparison Of Biophysical Techniques." M. W. Freyer. R. Buscaglia, Binh Nguyen, W. David Wilson and Edwin A. Lewis, Anal. Biochem., 355, 259 (2006).
"A High-Throughput, High-Resolution Strategy For The Study Of Site-Selective DNA Binding Agents: Analysis Of A Highly Twisted Benzimidazole-Diamidine." K. D. Goodwin, M. A. Lewis, Farial A. Tanious, Richard R. Tidwell, W. David Wilson, Millie M. Georgiadis and Eric C. Long, J. Am. Chem. Soc., 128, 7846 (2006).
"Synthesis And Evaluation Of An Intercalator-Polymide Hairpin Designed To Target The Inverted CCAAT Box 2 In The Topoisomerase Iialpha Promoter." L. V. Flores, A. M. Staples, H. Mackay, C. M. Howard, P. B. Uthe, J. S. Sexton, K. L. Buchmueller, W. David Wilson, C. O’Hare, J. Kluza, D. Hochhauser, J. A. Hartley and Moses Lee, Chembiochem., 7, 1722 (2006).
"Dicationic DNA-Targeted Antiprotozoal Agents: Naphthalene Replacement of Benzimidazole." S. Chackal-Catoen, Yi Miao, W. David Wilson, T. Wenzler, Reto Brun and David W. Boykin, Bioorg. Med. Chem., 14, 7434 (2006).
"Synthesis, DNA Affinity, And Antiprotozoal Activity Of Linear Dications: Terphenyl Diamidines And Analogues." Mohamed A. Ismail, Reem K. Arafa, Reto Brun, T. Wenzler, Yi Miao, W. David Wilson, C. Generaux, A. Bridges, J. Ed Hall and David W. Boykin, J. Med. Chem., 49, 5324 (2006).
"Synthesis And Antiparasitic Evaluation Of Bis-2,5-[4-Guanidinophenyl]Thiophenes." J. L. Gonzalez, C. E. Stephens, T. Wenzler, R. Brun, Farial A. Tanious, W. David Wilson, T. Barszcz, K. A. Werbovetz and David W. Boykin, Eur. J. Med. Chem., 42, 552 (2007).
"Binding Of Netropsin To Several DNA Constructs: Evidence For At Least Two Different 1:1 Complex Formed From An -AATT-Containing DNA Construct And A Single Minor Groove Binding Ligand." Matt W. Freyer, R. Buscaglia, D. Cashman, S. Hyslop, W. David Wilson, J. Brad Chaires and Edwin A. Lewis, Biophys. Chem., 126, 186 (2007).
"Diphenyl Furans And Aza Analogs: Effects Of Structural Modification On In Vitro Activity, DNA Binding, And Accumulation And Distribution In Trypanosomes." A. M. Mathis, A. S. Bridges, Mohamed A. Ismail, A. Kumar, I. Francesconi, M. Anbazhagan, Q. Hu, Farial A. Tanious, T. Wenzler, J. Saulter, W. David Wilson, R. Brun, David W. Boykin, Richard R. Tidwell and J. Ed Hall, Antimicrob Agents Chemother., 51, 2801 (2007).
"Biosensor - Surface Plasmon Resonance: Quantitative Analysis of Small Molecule - Nucleic Acid Interactions." Binh Nguyen, Farial A. Tanious and W. David Wilson, Methods, 42, 150 (2007).
"Synthesis And Biophysical Evaluation Of Minor-Groove Binding C-Terminus Modified Pyrrole And Imidazole Triamide Analogs Of Distamycin." T. Brown, Z. Taherbhai, J. Sexton, A. Sutterfield, M. Turlington, L. Stallings, K. Buchmueller, H. Mackay H, C. O'Hare, Binh Nguyen, W. David Wilson, Moses Lee and J. A. Hartley, Bioorg. Med. Chem., 15, 474 (2007)
"Unusually Strong Binding To The DNA Minor Groove By A Highly Twisted Benzimidazole-Diphenylether: Induced Fit And Bound Water." Farial A. Tanious, William Laine, Paul Peixoto, Christian Bailly, Kristie D. Goodwin, Mark A. Lewis, Eric C. Long, Millie M. Georgiadis, Richard R. Tidwell and W. David Wilson, Biochemistry, 46, 6944 (2007).
"Induced Fit Conformational Changes Of A 'Reversed Amidine' Heterocycle: Optimized Interactions In A DNA Minor Groove Complex." Manoj Munde, M. Lee, Stephen Neidle, Reem K. Arafa, David W. Boykin, Yang Liu, Christian Bailly and W. David Wilson, J. Am. Chem. Soc., 129, 5688 (2007).
"Break In The Heat Capacity Change At 303 K For Complex Binding Of Netropsin To AATT Containing Hairpin DNA Constructs." M. W. Freyer, R. Buscaglia, A. Hollingsworth, J. Ramos, M. Blynn, R. Pratt, W. David Wilson and E. A. Lewis, Biophys. J., 92, 2516 (2007).
"Structure-Specific Recognition Of Quadruplex DNA By Organic Cations: Influence Of Shape, Substituents And Charge." Elizabeth W. White, Farial Tanious, Mohamed A. Ismail, Anthony P. Reszka, Stephen Neidle, David W. Boykin and W. David Wilson, Biophysical Chemistry, 126, 140 (2007).
"High Affinity Homologous Peptide Nucleic Acid Probes For Targeting A Quadruplex Forming Sequence From A MYC Promoter Element." Subhadeep Roy, Farial Tanious, W. David Wilson, Danith H. Ly and Bruce A. Armitage, Biochemistry, 46, 10433 (2007).
"Sequence Recognition In The Minor Groove Of DNA By Covalently Linked Formamidoimidazole-Pyrrole-Imaidazole Polyamides: The Effect Of H-Pin Linkage And Linker Length On Selectivity And Affinity." C. C. O'Hare, P. Uthe, Hilary Mackay, Kevin Blackmon, Justin Jones, Toni Brown, Binh Nguyen, W. David Wilson, Moses Lee and John Hartley, Biochemistry, 46, 11661 (2007).
"Sequence And Length Dependent Thermodynamic Differences In Heterocyclic Diamidine Interactions At AT Base Pairs In The DNA Minor Groove." Yang Liu, A. Kumar, David. W. Boykin and W. David Wilson, Biophys. Chem., 131, 1 (2007).
"Design Of DNA Minor Groove Binding Diamidines That Recognize GC Base Pair Sequences: A Dimeric-Hinge Interaction Motif." Manoj Munde, Mohamed A. Ismail, Reem K. Arafa, Paul Peixoto, Catherine J. Collar, Yang Liu, Laixing Hu, M. H. David-Cordonnier, A. Lansiaux, Christian Bailly, David W. Boykin and W. David Wilson. J. Am. Chem. Soc., 129, 13732 (2007).
"Biosensor-Surface Plasmon Resonance Methods For Quantitative Analysis Of Biomolecular Interactions." Farial A. Tanious, Binh Nguyen and W. David Wilson, Methods Cell Biol., 84, 53 (2008).
"DNA Minor Groove Interactions Of Antiparasitic Diamidines: Reevaluation Of The Crescent-Shape Concept In Groove-Binding." Binh Nguyen, David W. Boykin and W. David Wilson in Synthetic and Biophysical Studies of DNA Binding Compounds (Editors: Moses Lee and Lucjan Strekowski) (2007).
"Targeting The Inverted CCAAT Box-2 Of The Topoisomerase Iialpha Gene: DNA Sequence Selective Recognition By A Polyamide-Intercalator As A Staggered Dimer." H. Mackay, T. Brown, J. S. Sexton, M. Kotecha, B. Nguyen, W. D. Wilson, J. Kluza, B. Savic, C. O'Hare, D. Hochhauser, M. Lee and J. A. Hartley, Bioorg. Med. Chem.,16, 2093 (2008).
"Synthesis And Antiprotozoal Activity Of Novel Bis-Benzamidino Imidazo[1,2-A]Pyridines And 5,6,7,8-Tetrahydro-Imidazo[1,2-A]Pyridines." M. A. Ismail, R. K. Arafa, T. Wenzler, R. Brun, F. A. Tanious, W. D. Wilson and D. W. Boykin, Bioorg. Med. Chem., 16, 683 (2008).
"Azaterphenyl Diamidines As Antileishmanial Agents." Laixing Hu, Reem K. Arafa, Mohamed A. Ismail, Tanja Wenzler, Reto Brun, Manoj Munde, W. David Wilson, Sandra Nzimiro, Serene Samyesudhas, Karl A. Werbovetz and David W. Boykin, Bioorg. Med. Chem. Lett., 18, 247 (2008).
"Inhibition Of HMGA2 Binding To DNA By Netropsin: A Biosensor-Surface Plasmon Resonance Assay." Yi Miao, Tengjiao Cui, Fenfei Leng, and W. David Wilson, Anal. Biochem., 374, 7 (2008).
"New Bis(2-Aminoimidazoline) And Bisguanidine DNA Minor Groove Binders With Potent In Vivo Antitrypanosomal And Antiplasmodial Activity." Fernando Rodriguez, Isabel Rozas, Marcel Kaiser, Reto Brun, Binh Nguyen, W. Wilson, Rory Garcia and Christophe Dardonville, J. Med. Chem., 51, 909 (2008).
"Antitumor Polycyclic Acridines. 20. Search For DNA Quadruplex Binding Selectivity In A Series Of 8,13-Dimethylquino[4,3,2-kl]acridinium Salts: Telomere- Targeted Agents." M. K. Cheng, C. Modi, J. C. Cookson, I. Hutchinson, R. A. Heald, A. J. McCarroll, S. Missailidis, F. Tanious, W. D. Wilson, J. L. Mergny, C. A. Laughton and M. F. Stevens, J. Med. Chem., 51, 963 (2008).
"Synthesis Of 4,8-Substitiutednaphtho[2,1-b]Thiophene Threading Intercalators." Sahar Badra, Mohamed M. El-Kerdawy, Farial A.Tanious, W. David Wilson and David W. Boykin, J. Heterocyclic Chem., 45, 123 (2008).
"Tri- And Tetra-Substituted Naphthalene Diimides As Potent G-Quadruplex Ligands." Francisco Cuenca, Olga Greciano, Mekala Gunaratnam, Shozeb Haider, Deeksha Munnur, Rupesh Nanjunda, W. David Wilson and Stephen Neidle, Bioorganic & Medicinal Chemistry Letters, 18, 1668 (2008).
"Antiparasitic Compounds That Target DNA." W. David Wilson, Farial A. Tanious, Amand Mathis, Denise Tevis, James Edwin Hall and David W. Boykin, Biochimie,90, 999 (2008).
"DNA Interactions Of Therapeutic Diamidine Compounds: Thermodynamics, Structure And The Role Of Water Molecules." Binh Nguyen, Stephen Neidle, and W. David Wilson, Accounts of Chemical Research, in press (2008).
"Direct Inhibition Of The DNA Binding Activity Of POU Transcription Factors Pit-1 And Brn-3 By Selective Binding Of A Phenyl-Furan-Benzimidazole Dication." Paul Peixoto, Yang Liu, Sabine Depauw, M. Hildebrand, David W. Boykin, Christian Bailly, W. David Wilson and Marie-Hélène David-Cordonnier, Nucleic Acids Research, 36, 3341 (2008).
"Novel Linear Triaryl Guanidines, N-Substituted Guanidines and Potential Prodrugs as Antiprotozoal Agents." Reem K Arafa, Mohamed A Ismail, Manoj Munde, W. D Wilson, Tanja Wenzler, Reto Brun and David W. Boykin, European Journal of Medicinal Chemistry, in press (2008).
"Modifying The N-Terminus of Polyamides: PyImPyIm Has Improved Sequence Specificity Over f-ImPyIm." Toni Brown, Hilary Mackay, Mark Turlington, Arden Sutterfield, Traci Smith, Alan Sielaff, Laura Westrate, Chrystal Bruce, Jerome Kluza, Caroline O'Hare, Binh Nguyen, W. David Wilson, John A. Hartley and Moses Lee. Bioorg. Med. Chem., 16, 5266 (2008).
"Influence Of DNA Structure On Adjacent Site Cooperative Binding." M. Rahimian, Y. Miao and W. D. Wilson, J. Phys. Chem. B., 112, 8770 (2008).
CURRENT RESEARCH GRANT SUPPORT:
National Institutes of Health: AI-064200; "Heterocycle Binding and Biology in the DNA Minor Groove."
National Institutes of Health: GM-61587; "Sequence-Specific Recognition of DNA by a Dimer Motif."
Gates Foundation: "DNA Targeted Drug Design for Infectious Diseases."
National Science Foundation: CHE 0414231; "Tuning the Thermodynamic and Kinetic Properties of the Binding of Polyamides to Their Cognate DNA Sequences."