Novel Bioactive Enzyme-DNA-Inorganic Materials

University Of Connecticut, Storrs CT

Investigators

Abstract

This award to University of Connecticut is funded by the Biomaterials program in the Division of Materials Research and co-funded by the Inorganic Bioinorganic Organometallic program in the Division of Chemistry. With this award, the PI will study enzyme-solid interactions at the molecular level using short strands of DNA to improve the catalytic properties of solid-bound enzymes, and will facilitate protein assembly in 3-dimensions along the DNA helices. Enzymes and proteins bound to short strands of DNA will be intercalated in the galleries of layered solids, Zirconium (IV) phosphate and phosphonates (ZrRPO3.nH2O, ZrRP). While the intercalation method is simple and facile, the covalent approach provides robust, reversible, indirect link between the solid and the protein. The nature as well as the strength of the enzyme-solid interactions will be optimized systematically by the chemical modification of the solid support surface functions, prior to DNA/enzyme binding. Nanobiomaterials prepared will be characterized in binding, XRD, SPR and calorimetry studies. Protein-DNA-solid contacts will be identified by protein cleavage studies, and the role of DNA in improving the bound protein properties will be investigated. Earlier studies have demonstrated that numerous enzymes and proteins have high affinity for double stranded DNA, and binding to DNA did not distort the protein structure or enzyme activity. The knowledge developed from these studies would be crucial for the rational design of new materials to maximize enzyme function. Enzymes are attractive biocatalysts, which show high chemo-, regio-, stereo-, and chiral selectivities, and enzymes are environmentally compatible. But the exciting possibility of using enzymes in the laboratory is severely limited due to the sensitivity of enzymes to the reaction conditions (pH, temperature, solvents, etc), high price, and limited availability. Immobilizing enzymes on solids can overcome some of these limitations. The PI is involved in educational outreach activities within and outside the university both at the graduate and undergraduate level. With this award, the PI will provide training and educational outreach integrated activities in Chemistry and Biology, including electron transport in biological systems, biomaterials, biocalorimetry and DNA/protein structures. These educational activities are expected to enrich the graduate, undergraduate, as well as high school students. As part of this award, the PI will continue to participate in the "Kids are Scientists Too" program, which was developed by the PIs department; the "Mentor Connection" program for high school students; and the NSF REU program (summer) as well as ChemIntern Program (academic year) for undergraduate students. The PI will continue to develop electronic courseware for the web to supplement graduate and undergraduate education courses.