James K. Bashkin
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. Dr. Bashkin moved from Monsanto to the Chemistry
faculty at Washington University in St. Louis, and subsequently
returned to industry at Monsanto (later Pharmacia and Pfizer).
He joined the faculty at UMSL in 1999. Dr. Bashkin started the
biotech company NanoVir, LLC in 2003 with Chris Fisher, and established
a research program at UMSL in July of 2004.
bashkinj@umsl.edu
Office Benton Hall 342
Tel: (314)516-7352
Fax: (314) 516-5342
Research
Interests
My group’s research has recently been directed to the
interface of chemistry and biology, in areas such as “chemical
genomics” and the design of antiviral and anticancer agents.
Much of this work involves the chemical synthesis and biochemical
testing of sequence-specific DNA binding molecules designed to
control gene expression. Our main goal is the invention of new
chemical methods to treat and diagnose diseases.
Most recently, we have explored bacterial cell-cell communication (quorum sensing), DNA-binding proteins and minor groove-binding polyamides that control of gene expression. As part of this work, we have developed methods for controlling delivery of polyamides to the nucleus of cells, controlling the expression of the COX-2 gene, and inhibiting replication of human papillomavirus (the major cause of cervical cancer).
An earlier
stage of our work was concerned with the design of ribozymes mimics:
molecules capable of sequence specific cleavage of RNA by the
natural transesterification/hydrolysis process. The applications
of such molecules include catalytic antisense agents that might
greatly enhance the efficiency of the antisense method for destruction
of target messenger RNA molecules of biochemical and medicinal
importance. We reported the first ribozymes mimic, which is shown
schematically in Fig. 1.
The chemical synthesis of the active DNA building block is shown next; ribozymes mimics are constricted by solid-phase synthesis of specific DNA sequences containing the thymidine analog that forms the active site when bound to a divalent metal ion:
In addition to this biological chemistry, I have maintained a strong interest in environmentally-benign organic chemistry, known as Green Chemistry. This work involved developing organic reactions that eliminated toxic waste associated with traditional processes.
Selected Recent Publications
"Polyamides for treating human papilloma virus". J. Bashkin, C. Fisher and K. J. Koeller, PCT Int. Appl. 2007, No. 103584, 90pp.
"Electrical signal-activated decontaminating coating, coating application, and articles protected by coatings". P. J. Kinlen, Y. Ding, J. K. Bashkin and S. Hou, Shifeng, U.S. Pat. Appl. Publ. (2007) 20pp.
"Ion-Exchange Chromatography Followed by ESI-MS for Quantitative Analysis of Sugar Monophosphates from Glucose Catabolism," J. J. Walters, M. A. Grayson, M. L. Gross, M. Hughes, G. Shearer, D. H. Kohl and J. K. Bashkin, J. Am. Soc. Mass Spec., 2006, 17, 104.
"Synthesis and evaluation of RNA transesterification efficiency using stereospecific serinol-terpyridine conjugates," W. C. Putnam and J. K. Bashkin, Nucleosides, Nucleotides & Nucleic Acids, 2005, 24, 1309.
"Controlling the intracellular localization of fluorescent polyamide analogs in cultured cells," K. S. Crowley, D. P. Phillion, S. S. Woodard, B. A. Schweitzer, M. Singh, H. Shabany, B. Burnette, P. Hippenmeyer, M. Heitmeier and J. K. Bashkin, Biorg. Med. Chem. Lett., 2003, 13, 1565.
"Structural Analysis of a Bacterial Quorum-Sensing Transcriptional Regulator Complexed with an Autoinducer Pheromone and Operator DNA," R. Zhang, T. Pappas, J. Wronski, N. R. De Lay, P. Miller, T. Oulmassov, J. M. Molyneaux, J. C. Anderson, J. K. Bashkin, S. C. Winans and A. Joachimiak, Nature, 2002, 417, 971.
"Efficient
new ribozyme mimics: direct mapping of molecular design principles
from small molecules to macromolecular, biomimetic catalysts," W.
C. Putnam, A. T. Daniher, B. N. Trawick and J. K. Bashkin, Nucleic Acids Research, 2001, 29, 2199.
"Probing
the Importance of Electrostatic Interactions of Ce(III) with
the Phosphodiester Backbone During Transesterification Using
Methylphosphonates," T. A. Osiek and J. K. Bashkin, New J. Chem. 2001, 25,
541.
"De
novo synthesis of artificial ribonucleases with benign metal
catalysts," W. C. Putnam and J. K. Bashkin, Chem. Commun., 2000, 767.
"Ribozyme
mimics: the evolution of gene-specific chemotherapy," T. A. Osiek,
W. C. Putnam and J. K. Bashkin, Editor: Torrence,
P. F. Biomed. Chem. 2000, 385. Publisher: John Wiley & Sons, Inc., New York, N. Y.
"Terpyridyl
Derivatives as Bifunctional Chelates. X-Ray Crystal Structures of 4'-(2-((1,3)dioxolane)ethyl)-2,2':6',2"-terpyridyl
thioether and [AuCl(4'-(methyl)-2,2':6',2"-terpyridyl thioether)](triflate)2," U.
Sampath, W.C. Putnam, T.A. Osiek, S. Touami, J. Xie, D. Cohen,
A. Cagnolini, P. Droege, D. Klug, C.L. Barnes, A. Modak, J.K.
Bashkin, S.S. Jurisson, Dalton Trans, 1999,
2049.
"Inorganic
Mimics of Ribonucleases and Ribozymes: From Random Cleavage to Sequence-Specific
Chemistry to Catalytic Antisense Drugs," B.N. Trawick, A.T.
Daniher, and J.K. Bashkin, Chem.
Rev., 1998, 98, 939.
"Precise
control of RNA cleavage by ribozyme mimics," A.T. Daniher and
J.K. Bashkin, Chem. Commun., 1998, 1077.
"Analysis
of Iron in Ferritin, the Iron-storage Protein: A
General Chemistry Experiment," M.J. Donlin, R.F. Frey, C. Putnam,
J. Proctor, and J.K. Bashkin, J. Chem. Educ., 1998, 75, 437.