Dendrimer Structure and Enzyme Activity

David Nowack (Chemistry)

Preliminary investigation into the relationship between dendrimer structure and enzyme activity

Dendrimers are highly branched, synthetic polymers that are mono-dispersant (narrow molecular weight range) and symmetrical macromolecules. First synthesized in the 1970s by Donald Tomalia and co-workers, dendrimers can be based on practically any type of chemistry, the specifics of which determine its solubility, degradability and biological activity. Because their structure can be precisely controlled, dendrimers have generated interest in biology and medicine as novel materials that may enhance specific goals in medicine and pharmaceutical sciences.

A fundamental uncertainty with using dendrimers in medicine is their unknown toxicity toward the cell. One measure of cellular toxicity is the inhibition of the activity of a cellular enzyme in the presence of the dendrimer. Given the large number of classes of enzymes (transferases, oxidoreductases, etc.) and the enormous number of dendrimers variants, the task of verifying the presence of inhibition is daunting. Yet, given a ready supply of dendrimers and a supply of purified enzymes in the different classes, this task is do-able and can have an important impact on their use in medicine. This project is to detect the inhibition of enzyme activity, if any, by dendrimers.

The Department of Chemistry and Biochemistry received a supply of dendrimer variants two years ago as the Department established a business of dendrimer production and distribution. With this relatively inexpensive supply of dendrimers and the funding to purchase purified enzymes from commercial vendors, the project being funded by this grant will begin to build a comprehensive database of dendrimer/enzyme behavior that had direct application to human medicine and, also, that examines the toxicity of nanomaterials at the molecular level.