Research Topics
Department of Chemistry
Ph.D. (1972) Sheffield University, UK
Research Topics
Research Interests
Our group is interested in using NMR and computational/quantum chemical methods to investigate protein structure and function with particular emphasis on designing new chemotherapeutic agents. WE are interested in cancer and in infectious diseases caused by protozoa, such as malaria and sleeping sickness, as well as bacterial infections, such as tuberculosis, tularemia and plague. In the past 2 years we have identified a series of novel chemo-therapeutic agents, bisphosphonates, which have a broad spectrum of activity as anti-parasitics and cures of several diseases have recently been obtained in animal models. These disease afflict well over 500 million individuals world-wide, and malaria and tuberculosis are becoming resistant to conventional drugs, making the development of new treatments of considerable importance.
The group is now interested in further developing these new lead bisphosphonates and we are using a combination of solid and liquid state NMR, together with computational/quantum chemistry, to help engineer more effective drugs by using QSAR (quantitative structure activity relationships) to guide the production of new molecules. NMR spectrometers operating at up to 750 MHz together with a cluster of about 60 CPUs are used in the group to facilitate this work (see http://feh.scs.uiuc.edu for more details). We also use NMR to study the metabolic pathways in pathogenic micro-organisms, which guides us to the discovery of new enzymes (drug targets), in addition to carrying out very basic studies of how some enzymes function and how they are inhibited by drug molecules. We are also involved with using quantum chemical methods to predict NMR and Mössbauer spectra of proteins, in order to learn more about electronic structure, as well as to provide additional probes of how drugs bind to enzyme active sites.
In very recent work, it has also been shown that the compounds we are investigating ("phosphoantigens") have profound effects on immune system, where they stimulate a subset of T cells to kill pathogens. These T cells have also been shown to be cytotoxic to human tumor cells, and the antigens are being developed for cancer chemotherapy. We are investigating structure-activity relationships with these molecules and are designing and making novel species which can be used to treat both infectious diseases and some tumors.
Key Words Chemotherapy,
Immunotherapy, Computational Chemistry, NMR
Current Research Funding NIH, NSF, UI, Industry, Heart
Association