Regulatory mechanisms have been found to be subject to considerably greater variation among species than the ordinary metabolic reactions. Thus it was suspected, and has indeed been established in a few instances, that the regulatory mechanisms are potential targets for the action of chemotherapeutic agents. Furthermore, regulatory metabolites and their analogues have also been found to have chemotherapeutic potential. We wish to exploit several examples of these kinds of relationships: The adenine nucleoside-XMP aminase interaction is believed to represent a newly recognized type of regulatory mechanism; the conformational change in the aminase ensuing from the interaction influences the rate of synthesis of the aminase molecule. This enzyme is a target for antitumor agents, but the most effective of these agents have unacceptable toxic effects. Thus, our studies on the properties of the aminase and its conformative responses, which underlie its sensitivity to inhibition, will be explored for the purpose of developing alternative inhibitors of a reaction already known to be critical for tumor cells. Another potential chemotherapeutic agent has emerged from our studies on the mode of action of indole-3-acetic acid, a plant auxin. The active metabolite of indole-3-acetic acid, 3-methyleneoxindole, has been shown to be bactericidal and to inhibit animal viral replication without cyto-pathogenic effects. It is another objective of this project to evaluate 3-methyleneoxindole as an antiviral agent and to elucidate its mode of action.
NIH ExPorter
NIH ExPorter