The completion of the human genome sequence has sparked intense investigation toward decoding the human proteome. Unfortunately, current methods for elucidating protein structure and function are time intensive and not practical for evaluating large proteomes. Protein microchips, where various proteins are arrayed on a surface and then analyzed for interaction with small molecules or other proteins, may provide a much-needed high-speed analysis tool. However, the fabrication of protein arrays including their respective protein immobilization strategies are still at an early stage of development.
The aim of the proposed research is to develop an entirely new method for immobilizing proteins onto various surfaces. Using auxtotropic bacterial strains, natural amino acids within a protein will be substituted with synthetic analogs. The analogs are predesigned to contain a reactive chemical group that will later be exploited to couple the protein to a functionalized surface using aqueous-phase, metal-mediated catalysis. In addition, a strategy for studying the dynamics between surface-bound proteins and various substrates is presented and provides the basis for array fabrication. In a broader sense, the proposed research attempts to integrate the strongest attributes of organometallic chemistry, materials science, and biology.
