Research Interests

 

I generally have opportunities for undergraduate and graduate students, pending resource availability.  Undergraduate students can get course credit or work for pay (when available).  Graduate students in the chemistry department who are interested in research can come by and talk to me to discuss opportunities and funding status.  All interested students are invited to come by my office or e-mail me.

 

Summary:  My research interests are diverse but focus primarily on DNA damage and/or protein binding by drugs and toxic substances.  Experimentally, we use a variety of techniques, including:  basic organic and inorganic synthesis, NMR spectroscopy, mass spectrometry, gel electrophoresis, HPLC, and computer (molecular mechanics) calculations. 

Interaction of platinum compounds with DNA and/or protein residues

Cisplatin, cis-Pt(NH3)2Cl2, is a widely used anticancer drug.  It has shown remarkable success with certain types of cancers, namely testicular and ovarian cancers.  Oxaliplatin is a third-generation drug that has been approved for colorectal cancers.  Thus, the reactions of platinum compounds with biological targets are of significant biological interest.  Reaction can occur with DNA, RNA, or proteins, the former being the key target responsible for anticancer activity. 

We are studying the effects of the size and shape of the platinum complex on the formation of DNA and protein adducts.  We have developed parameters that will allow us to use molecular mechanics calculations to generate computer models of complexes between platinum and methionine residues (a key amino acid target in proteins), and we are using parameters developed previously for platinum and guanine (the primary site of platinum reaction in DNA).  These calculations are being used to predict the effect of the size of the platinum complex on the stability of guanine and methionine complexes. 

Experimentally, we have synthesized selected cisplatin analogs.  We have reacted these analogs with amino acid and nucleotide derivatives and characterized the products, primarily with NMR spectroscopy, HPLC, and LC/MS.  We will be testing the biological activity of many of these compounds to look for trends in toxicity and/or cellular uptake.

Collaborators:  Dr. Blairanne Williams (WKU), Dr. Michael Smith (WKU)

Stabilization of polyunsaturated fatty acids

 

In collaboration with Dr. John Khouryieh (Principal Investigator), we are looking at methods to stabilize polyunsaturated fatty acids for food applications.  This project utilizes a number of different techniques combining both chemistry and food science research areas.