Responsive Polymer-Engineered Protein Conjugates

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DESCRIPTION (provided by applicant): The long term objective of our research is to develop new compositions and technologies for controlling biomolecular recognition processes in the rapidly developing fields of micro- and nano-scale sensing and diagnostic devices. In the first eight years of this research program, we have developed a new approach to the control of biomolecular recognition that is based on coupling the stimulated collapse (dehydration) or expansion (rehydration) of the "smart" polymer coil with recognition events such as protein-ligand, enzyme-substrate, protein-protein and DNA hybridization reactions. In this approach, the smart polymers serve as both antennae and actuators, to sense signals and respond to them, leading to control of biorecognition events. Their characteristic sharp responses in coil size and physical properties to small changes in pH, temperature, and/or electromagnetic irradiation over narrow ranges or at specific wavelengths permits rapid and precise control of molecular events. We term this a "molecular switch". We seek here to continue the development and applications of such molecular switches with affinity proteins, ligands and enzymes, as well as to develop new strategies for releasing captured targets on command, and for "molecular matchmaking" that selectively and reversibly brings together specific, interactive molecular components in complex mixtures. The molecular engineering underlying these aims spans sophisticated polymer design and synthesis and protein and DNA engineering, and matches the functional properties of the stimuli-responsive polymers to the molecular complexities of ligand binding pockets, active sites, and receptor-ligand sequences.