个人简介

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

研究领域

Organic, Biochemistry, Inorganic

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. Bashkin pic1.png 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. Bashkin pic 2.png 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.

近期论文

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"Ogawa, D., Saraf, I., Sra,A., Timmons, R., Goeckner, M., and Overzet, L. “The direct injection of liquid droplets into low pressure plasmas”, J. Vac. Sci. & Technology, A, 27: 342-351,2009 Bhattacharyya, D.,Yoon, W.-J., Berger, P.R., Timmons, R.B. “Plasma-polymerized multistacked organic bipolar films: A new approach to flexible high-k dielectrics“, Advanced Materials, 20: 2383-2388,2008 Thevenot , P., Cho, J., Wavhal, D., Timmons, R.B., Tang., L. “Surface chemistry influences cancer killing effect of TiO2 nanoparticles“, Nanomedicine : Nanotechnology, Biology, and Medicine, 4: 226-236,2008 Kamath, D., Bhattacharyya , D., Padukudru , C., Timmons, R.B., Tang, L. “Surface chemistry influences implant-mediated host tissue responses“, J.Biomed. Maters. Res. Part A, 86: 617-626, 2008 Chapman, C.L., Bhattacharyya, D., Eberhart, R.C., Timmons, R.B., Chuong, C. “Plasma polymer thin film depositions to regulate gas permeability through nanoporous track etched membranes“, J. of Membrane Science, 318: 137-144, 2008 Dennis, B.H., Jin, W., Cho,J., Timmons, R.B. “Inverse determination of kinetic rate constants for transesterification of vegetable oils“, Inverse Problems in Science and Engineering, 16: 693-704, 2008 Nair, A., Zou, L., Bhattacharyya, D., Timmons, R. B., Tang, Liping. “Species and density of implant surface chemistry affect the extent of foreign body reactions“, Langmuir, 24: 2015-2024,2008 Bhattacharyya, D., Pillai, K., Chyan O., Tang L., Timmons R.B. “A new class of thin film hydrogels produced by plasma polymerization“, Chemistry of Materials, 19: 2222-2228,2007 Xu, Y.; Berger, P.R.; Cho, J.; Timmons, R.B. “Pulsed plasma polymerized dichlorotetramethyl-disiloxane high-k gate dielectrics for polymer field-effect transistors“, Journal of Applied Physics, 99: 1-4, 2006 Cho, J.; Denes, F.S.; Timmons, R.B. “Plasma processing approach to molecular surface tailoring of nanoparticles: Improved photocatalytic activity of TiO2“, Chemistry of Materials, 18: 2989-2996, 2006 Ma Y.; Manolache, S.; Denes, F.S.; Cho, J.; Timmons, R.B. “Surface modification of rutile TiO2 by submerged arc discharge for improved photoreactivity“, Journal of Materials Engineering and Performance, 15: 370-375, 2006 Susut C.; Timmons, R.B. “Plasma enhanced chemical vapor depositions to encapsulate crystals in thin polymeric films: A new approach to controlling drug release rates“, International Journal of Pharmaceutics, 288:253-261, 2005 Li, M.L.; Timmons, R.B.; Kinsel, G.R. “Radio frequency plasma polymer coatings for affinity capture MALDI mass spectrometry“, Analytical Chemistry, 77: 350-353, 2005 Xu Y.F., Berger, P.R., Cho, J., Timmons, R.B. “Capacitance-voltage characterization of pulsed plasma polymerized allylamine dielectrics for flexible polymeric field effect transistors“, Journal of Electronic Materials, 33: 1240-1247, 2004" “Compounds for treating papilloma virus infection,” J. K. Bashkin, K. J. Koeller, T. G. Edwards and C. Fisher, US Pat. 2015, No. 8,993,609, App. No.13/357,740 "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; in press ″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 “Binding studies of a large antiviral polyamide to a natural HPV sequence”, G. He, E. Vasilieva, G. D. Harris, K. J. Koeller, J. K. Bashkin and C. M. Dupureur, Biochimie 2014, 102, 83. ”Compounds for treating papilloma virus infection”, J. K. Bashkin, K. J. Koeller, T. G. Edwards and C. Fisher, PCT Int. Appl. 2014, WO 2014065848; A2 20140501. ″Modulation of DNA-polyamide interaction by β-alanine substitutions: a study of positional effects on binding affinity, kinetics and thermodynamics″, S. Wang, K. Aston, K. J. Koeller, D. G. Harris, N. P. Rath J. K. Bashkin and W. D. Wilson, Org. & Biomol. Chem. 2014, 12, 7523