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Dr. Bashkin received his B.A. in Chemistry from the University of California, Irvine, and his D.Phil. from Oxford, England. He was an NIH postdoctoral fellow at Harvard before joining Monsanto Corporate Research. He spent time with both Washington University and then again Monsanto (later Pharmacia and Pfizer) prior to joining UMSL in 1999 where he is now Professor of Chemistry and Biochemistry. |
bashkinj@umsl.edu Office: B 221 |
Research Interests
My group’s research has recently been directed to the interface of chemistry and biology, in areas such as "chemical genomics," the design of antiviral and anticancer agents and Green Chemistry. Much of this work involves the chemical synthesis and biochemical testing of sequence-specific DNA binding molecules designed to control gene expression. Our main goals are the invention of new chemical methods to treat and diagnose diseases and the invention of new chemical reactions to eliminate toxic waste and other undesirable features of traditional chemistry.
Recently, we have worked toward prevention of cervical cancer. Most cervical cancer is caused by certain "high-risk" forms of Human Papillomavirus (HPV), primarily HPV16 and 18. We have designed potential antiviral agents that successfully eliminate HPV16 DNA from human cells in culture, with pseudo-IC50 values as low as 8 nM. Pyrrole-imidazole polyamides are used to target viral DNA sites such as the one shown below, bound to a DNA target. We have expanded our work to HPV18; all drug discovery and development have been collaborations with Dr. Chris Fisher of NanoVir LLC. Studies of the biophysics of polyamides interacting with HPV DNA have been collaborations with Dr. Cynthia Dupureur of this department.
All of our antiviral polyamides have been rather large molecules. Their binding to DNA has been studied with DNase I footprinting and EDTA-polyamide affinity cleavage, both via capillary electrophoresis.
To study the biophysics of smaller polyamides, both to help understand the larger polyamides and to design better leads for other human diseases, we have collaborated with biophysicist W. David Wilson of Georgia State University for several years.
Earlier work was concerned with the design of ribozymes mimics: molecules capable of sequence specific cleavage of RNA by the natural transesterification/hydrolysis process. Applications include catalytic antisense agents that destroy target messenger RNA without requiring RNase H activation. We reported the first ribozymes mimics made with metal comlexes and DNA.
In addition to this biological chemistry, I have maintained a strong interest in environmentally-benign organic chemistry, known as Green Chemistry. This work involves developing organic reactions that eliminated toxic waste associated with traditional processes.
Selected Recent Publications
"Size matters: DNA binding site kinetics as a function of polyamide size," J.Niederschulte, Y. Song, J. K. Bashkin and C. M. Dupureur, Biochimie, 2022, 199, 123.
″Oligonucleotides containing abasic threoninol-terpyridine residues as potential artificial ribonucleases,″ W. C. Putnam and J. K. Bashkin, J. Inorg. Biochem.2022, 232, 111831.
″DNA binding site kinetics of a large antiviral polyamide,″ J. Niederschulte, Y. Song, A. H. Park, J. K. Bashkin and C. M. Dupureur, Biochemie, 2021, 185, 146.
″Compositions and methods for treatment of Bowen's disease and related diseases,″ J. E. Obi and J. K. Bashkin, Pat. Appl. 2019, WO 2019059943.
″Modulating DNA by polyamides to regulate transcription factor PU.1-DNA binding interactions″, B. Liu, J. K. Bashkin, G. M. K. Poon, S. Wang, S. Wang and D. W. Wilson, Biochimie, 2019, 167, 1
″DNA binding thermodynamics and site stoichiometry as a function of polyamide size″, Y. Song, J. Niederschulte, K. N. Bales, A. H. Park, J. K. Bashkin and C. M. Dupureur, Biochimie, 2019, 165, 170
″Thermodynamics and site stoichiometry of DNA binding by a large antiviral hairpin polyamide,″ Y. Song, J. Niederschulte, K. N. Bales, J. K. Bashkin and C. M. Dupureur, Biochimie, 2019, 157, 149
″A Polyamide Inhibits Replication of Vesicular Stomatitis Virus by Targeting RNA in the Nucleocapsid,″ R. H. Gumpper, W. Li, C. H. Castañeda, M. J. Scuderi, J. K. Bashkin, M. Luo, J. Virol, 2018, 92, 00146
″β-Alanine and N-terminal cationic substituents affect polyamide-DNA binding,″ B. Liu, S. Wang, K. Aston, K. J. Koeller, S. F. H. Kermani, C. H. Castaneda, M. J. Scuderi, R. Luo, J. K. Bashkin and D. W. Wilson, Org. & Biomol. Chem., 2017 15, 9880.
″Improved Antiviral Activity of a Polyamide Against High-Risk Human Papillomavirus Via N-Terminal Guanidinium Substitution,″ C. H. Castaneda, J. M. Scuderi, T. G. Edwards, G. D. Harris, C. M. Dupureur, K. J. Koeller, C. Fisher and J. K. Bashkin, MedChemComm. 2016, 7, 2076.
″Interactions of two large antiviral polyamides with the long control region of HPV16,″ E. Vasilieva, J. Niedershulte, Y. Song, J. K. Bashkin and C. M. Dupureur, Biochemie, 2016, 127, 103
″What is the antiviral potential of pyrrole-imidazole polyamides?″ G. He and J. K. Bashkin, Fut. Med. Chem., 2015, 7, 1953
″Guanidinyl-substituted polyamides useful for treating human papilloma virus″, J. K. Bashkin, T. G. Edwards, C. Fisher, G. D. Harris, Jr. and K. J. Koeller, US Patent 9,133,228, issued 9/15/2015.
"Heterogeneous dynamics in DNA site discrimination by the structurally homologous DNA-binding domains of ETS-family transcription factors″, G. He, A. Tolic, .J. K. Bashkin and G. M. K. Poon, Nucleic Acids Res. 2015. 43, 4322.
″DNA binding polyamides and the importance of DNA recognition in their use as gene-specific and antiviral agents″, K. J. Koeller, G. D. Harris, K. Aston, G. He, C. H. Castaneda, M. A. Thornton, T. G. Edwards, S. Wang, R. Nanjunda, D. W. Wilson, C. Fisher and J. K. Bashkin, Med. Chem. 2014, 4, 338
