Current projects are outlined below. Enzyme catalyzed aromatic substitution. The catalytic properties of iodotyrosine deiodinase are currently under investigation to identify the source of its unique reactivity. This enzyme is one of only two types of mammalian enzymes known to effect reductive iodide elimination, and thus it provides a superb model for investigating the chemical basis of metabolic diversity within organisms. Structural determinants of DNA modification under physiological conditions.
Genetic changes caused by environmental risks occur along sequences of DNA at highly variable rates.
Often the majority of modifications is found in a very limited number of sites that are referred to as hotspots. The molecular basis of this observation is the subject of intense study. We are examining both oligonucleotide and polynucleotide models to identify the major determinants of genetic damage induced by ultraviolet light. This reaction is central to the action of many anti-cancer drugs despite its inherent lack of specificity. Most efforts to enhance selectivity have relied on the technique of affinity modification in which an electrophile is attached to a DNA-binding ligand.