B.S. 1966, University of North Carolina, Chemistry
Ph.D. 1970, Purdue University, Biophysical Chemistry
Biophysical Chemistry; interaction of small molecules with nucleic acids and nucleic acid molecular recognition; thermodynamic analysis of nucleic acid complexes; structure-activity relationships; binding, kinetic, and conformational analyses of drug, peptide and protein complexes with DNA and RNA; experimental and molecular modeling methods in nucleic acid conformational analysis and drug design. We use spectroscopy, NRR, mass
spectrometry, biosensor surface plasmon resonance, ITC and others.
All of the projects in my laboratory focus on the structure, interaction and 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 and structures of DNA or RNA. We have designed biologically active compounds that target unusual DNA structures and important protein-DNA complexes for control of gene expression. A range of solution and molecular modeling experiments are being conducted on complexes of compounds that interact with DNA oligomer sequences that mimic selected sequences from the organism to be targeted. These studies provide information for 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 have recently solved the NMR structure of a new compound that recognizes mixed sequences of DNA with a water mediated H-bond. 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 compounds with DNA and we have new designs that can recognize a number of DNA sequences and structures with high specificity.
Recent publications: A few examples out of a total of over 400 publications:
“Compound Shape Effects in Minor Groove Binding Affinity and Specificity for Mixed Sequence DNA.” Paul Guo P, A. A. Farahat, Ananya Paul, Narinder K. Harika, David W. Boykin, W David Wilson, J Am Chem Soc. 140, 14761-14769 (2018).
“Bound Compound, Interfacial Water, and Phenyl Ring Rotation Dynamics of a Compound in the DNA Minor Groove. ” Narinder K. Harika, W David Wilson, Biochemistry. 57, 5050-5057 (2018).
“Electrostatic Control of DNA Intersegmental Translocation by the ETS Transcription Factor ETV6.” Tam Vo, S. Wang, Gregory Poon, W. David Wilson, J. Biol. Chem. 292, 13187-13196 (2017).
“First Structure of a Designed Minor Groove Binding Heterocyclic Cation that Specifically Recognizes Mixed DNA Base Pair Sequences”. N.K. Harika, M.W. Germann, W. David Wilson, Chemistry 23, 17612-17620 (2017).
“Systematic Synthetic and Biophysical Development of Mixed Sequence DNA Binding Agents”. Paul A, Kumar A, Nanjunda R, Farahat AA, Boykin DW, Wilson WD, Org Biomol Chem. 15, 827-835 (2017).
“DNA Microstructure Influences Selective Binding of Small Molecules Designed to Target Mixed-site DNA Sequences.” Laughlin-Toth, Sarah; Carter, E. Kathleen; Ivanov, Ivaylo; Wilson, W. David, Nucleic Acids Res. 45, 1297-1306 (2017).
” Inhibition of the myeloid master regulator PU.1 as a therapeutic strategy in acute myeloid leukemia,” Iléana Debré, J. Leite, Ananya Paul, Hye Mi Kim, A. Kumar, A Farahat, B. Bartholdy, Kelly Mitchell, Luis Carvajal, J. Chen, Amit Verma, B. Will, David W Boykin, W. David Wilson, Gregory M. Poon, Ulrich Steidl, Inhibition of the myeloid master regulator PU.1 as a therapeutic strategy in acute myeloid leukemia, J Clinical Invest. 127, 4297-4313 (2017).