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R. Bruce Banks

Bruce Banks
Title Associate Professor
Expertise Biorganic, Chemistry
Education B.S., Vanderbilt University, 1970
Ph.D., Florida State University, 1976
Postdoctoral Fellow,  Vanderbilt University Center in Molecular Toxicology, 1976-1978
University of Minnesota Department of Pharmacology, 1978-1980
Office Sullivan Science Building, Rm 415
Phone 336.334.4606
E-Mail Email Dr. Banks

Drug design based on inhibition of molybdenum hydroxylases. 

The molybdenum hydrxoxylases, xanthine oxidase and aldehyde oxidase, are known to participate in the metabolism of numerous drugs including antitumor agents.  Inhibitors of these enzymes are useful in prolonging the therapeutic efficacy of antitumor agents and in prevention of oxidative stress associated with action of the enzymes.  Preliminary experiments in our lab have established that several nitroaromatic compounds, including 2-, 3-, and 5-nitrobenzaldehyde, are potent inhibitors of rabbit liver aldehyde oxidase. We hope to identify similar compounds which have even greater inhibitory activity toward the enzyme. Such inhibitors would be useful experimental tools for study of the enzymes, as well as potential lead compounds for drug development. Data from these experiments will be used to determine whether hydrophobic or more polar interactions are necessary for optimal interaction between inhibitor and enzyme. A critical glutamate and its interaction with substrates/inhibitors of aldehyde oxidase guides our thinking in the design of new inhibitors,  We believe that the similar electronic character of the carboxylate and nitro groups may partially explain why nitraromatic compounds are potent inhibitors of aldehyde oxidase. In order to test this hypothesis, we will compare the enzyme inhibitory activity of structurally similar compounds containing either the carboxy or nitro functional group.  Experiments to determine whether inhibitors interact with the molybdenum site or, alternatively, with other redox sites.

Enzymatic catalysis by enzymes in organic solvent media.

In the past, enzymes were viewed as being incompatible with the organic solvents used in conventional synthetic procedures. However, in recent years a remarkable number of synthetic transformations have been carried out with enzymes suspended in organic solvents containing very low water content (<5%). Enzymatic reactions in nonaqueous media provide several advantages when compared with their aqueous counterparts: (1) the enzyme, which is insoluble in organic solvents, may be separated by filtration from solvent-soluble reaction products, (2) compounds which are insoluble in water may be used as substrates for reaction, (3) reactions with unfavorable equilibria in water, such as condensations reactions, may be accomplished, and (4) enzymes often display altered selectivities and enhanced thermal stabilities in organic solvents. Lipases and other hydrolytic enzymes are particularly robust enzymes in organic solvents and have been extensively investigated. Other families of enzymatic catalysts have received less attention. We have shown that aldehyde oxidase can catalyze several synthetically useful oxidations when conducted in water-immiscible organic solvents such as dichloromethane and hexane containing 3% water or less. For example, the enzyme suspended in dichloromethane converts phenazine methosulfate to a ring-oxidized product, 2-methylbutanal to 2-methylbutanoic acid , and phenanthridine to phenanthridone.  These reactions, carried out on a micromolar scale, demonstrate the potential utility of oxidations by aldehyde oxidase in organic solvents. We are now scaling up these nonaqueous enzyme-catalyzed reactions to synthetically useful proportions, i.e., milligram to gram quantities of reactants.

REPRESENTATIVE PUBLICATIONS

Banks, R.B., and Cooke, Jr. R.T., Biochem.Biophys.Res.Commun.1986137, 8-14. "Chromate Reduction by Rabbit Liver Aldehyde Oxidase".

Banks, R.B. and Barnett, S.D., Biochem.Biophys.Res.Commun.1986140, 609-615.  "Tropylium Tetrafluoroborate, A Novel Substrate for Aldehyde Oxidase".