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B.Sc (McGill University, 1962) Ph. D. (California Institute of Technology, 1967) Postdoctoral Fellow (Stanford University, 1967-68)

研究领域

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Chemical Biology Chemical Physics

Research activity continues in studies on the phosphorescence of proteins in solution at room temperature initiated in this laboratory a number of years ago. While chromophores free in solution in the absence of O2 possess very short lifetimes, tryptophan residues buried within the folds of the polypeptide chains of globular proteins can display room temperature phosphorescence (RTP) with lifetimes that are hundreds of milliseconds to seconds in duration. In O2-free solutions the lifetimes can vary over at least a range of 104 depending on the flexibility of the local structure, so that the lifetimes provide a very sensitive measure of the protein flexibility. We have used site-directed mutagenesis to identify the particular amino acid side chain responsible for the long-lived emission, and have shown that a Trp residue displaying RTP can be introduced into a protein. Work is continuing on the mechanism that relates the lifetimes with the precise dynamic events with the structure. Work is being carried out in collaboration with C. Williams and Prof. G.R. Brown on the interaction of bile salts with cationic polymer resins. This work is part of an ongoing search for polymeric resins that would effective in the elimination of bile acids from the digestive tract in the treatment of hypercholesterolemia. The present work is directed toward elucidating the enthalpic and entropy contributions involved in the binding interactions to provide a molecular basis for the generation of polymers that will prove particular effective as adsorbents under physiological conditions. There is also an ongoing interest in the generation of demonstrations that can be used effectively to assist undergraduate students in developing an intuitive grasp of traditionally difficult concepts in physical chemistry at the introductory level. Work, for example, is continuing on a demonstration and accompanying computer program employing weights and elastics that has proven particularly effective in illustrating the principles of chemical thermodynamics.

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