Scott Singleton, PhD

RESEARCH INTERESTS:

The Singleton Laboratory is interested in understanding the molecular basis for the develoment and transmission of microbial drug resistance and the discovery and exploitation of new strategies for controlling drug-resistant microorganisms. We develop and adapt synthetic chemistry and synthetic biology methods to provide new molecular tools – both biologically active small molecules and innovative platforms – for hypothesis-driven biological research and pharmaceutical discovery. This important foundation of our program offers both chemically-oriented and biologically-oriented researchers new opportunities for the development of integrated, multi-disciplinary knowledge and technologies.

Tools

* chemical synthesis
* synthetic biology
* combintorial biochemistry
* molecular biophysics
* high-throughput screening

To Study

* synthetic nucleotide analogs, designed peptides, organometallic complexes
* DNA repair and recombination related to drug resistance
* genomic approaches for revealing antibacterial drug targets
* designed genetic selections for directed evolution of unnatural enzymes

To Understand

* molecular mechanisms related to the evolution of drug resistance
* protease inhibitor resistance in human viruses

To Discover

* new antimicrobial targets and strategies
* new paradigms for antimicrobial drug development
* new lead compounds via HTS
* new macromolecular therapeutics
* new enzymes

RECENT PUBLICATIONS:

Lee, A.M., Wigle, T.J., and Singleton, S.F.*, “Two-Tiered High-Throughput Screening-Compatible Assay for Inhibitors of RecA Activities,” Analytical Biochemistry (in press).

Wigle, T.J., and Singleton, S.F.*, “Directed Molecular Screening for RecA ATPase Inhibitors,” Bioorganic & Medicinal Chemistry Letters, DOI 10.1016/j.bmcl.2007.04.013 (2007).

Cline, D.J., Holt, S.L., and Singleton, S.F.*, “Inhibition of Escherichia coli RecA by a Rationally Redesigned Helical Peptide,” Organic & Biomolecular Chemistry, DOI DOI: 10.1039/B703159A (2007).

Singleton, S.F.*, Roca, A.I., Lee, A.M., and Xiao, J., “Probing the Structures of RecA-DNA Filaments. Advantages of a Flurescent Guanine Analog,” Tetrahedron 63: 3553-3566 (2007).

Lee, A.M., Xiao, J., and Singleton, S.F.*, “Origins of Sequence Selectivity in Homologous Genetic Recombination: Insights from Rapid Kinetic Probing of RecA-mediated DNA Strand Exchange,” Journal of Molecular Biology 360: 343-359 (2006).

Xiao, J., Lee, A.M., and Singleton, S.F.*, “Direct evaluation of a kinetic model for RecA-mediated DNA strand exchange: Importance of nucleic acid dynamics and entropy during homologous genetic recombination,” ChemBioChem 7: 1265-1278 (2006).

Lee, A.M. and Singleton, S.F.*, “Intersubunit Electrostatic Complementarity in the RecA Nucleoprotein Filament Regulates Nucleotide Substrate Specificity and Conformational Activation,” Biochemistry 45: 4514-4529 (2006).

Wigle, T.J., Lee, A.M., and Singleton, S.F.*, “Conformationally Selective Binding of Nucleotide Analogs to Escherichia coli RecA: A Ligand-Based Analysis of the RecA ATP-Binding Site,” to Biochemistry 45: 4502-4513 (2006).

Xiao, J., Lee, A.M., and Singleton, S.F.*, “Construction and Evaluation of a Kinetic Scheme for RecA-mediated DNA Strand Exchange,” Biopolymers 81: 473-496 (2006).