Bioorganic Methodology to Create Novel Biomolecular Platforms to Address Critical Needs in Molecular Recognition and Function

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This research program focuses on the creation of novel biomolecular scaffolds that will become key elements in the chemical design of selective affinity receptors for small organic and inorganic molecules as well as unique molecular frameworks useful in controlling macromolecule interactions with chemical surfaces and advanced materials. The creation of innovative molecular recognition systems is a critical enabling technology that underpins the development of new materials and therapeutic agents for society. Chemical and biochemical manipulation of complex multisubunit proteins and viruses will be undertaken to serve as unique, self-assembling biomolecular platforms valuable for materials and biomaterials science. Currently intense interest is being directed toward the application of large multisubunit proteins and viruses to the synthesis of molecular scaffolds able to "hang and orient" photovoltaic systems, or to serve as building blocks for the fabrication of biomolecular batteries, novel biofibers or drug delivery systems. Hence there is exceptional need for developing the chemistry of these complex structures and to train the next generation of scientists to contribute to the application of renewable biosystems to materials science, energy systems and therapeutics. Various levels of biomolecular complexity will be explored by these chemical approaches. These include:***A) Chemical manipulation and protein engineering of cavity-containing multisubunit spherical proteins which range in complexity (24 to 180 protein subunits), mass (440 kDa to 6.9 MDa) and diameter (120-320 Å). Our research program in this area is to develop new ways to control their inner and outer molecular surfaces as well as to develop approaches to create new host-guest macromolecular complexes using engineered protein components.***B) Development of bioorganic approaches to create novel "virus-based molecular platforms" (linear bacteriophage M13, ~ 2770 protein subunits, ~ 60 Å in diameter and ~ 1 micron in length; mass 16.8 MDa) to serve as unique biomolecular scaffolds potentially useful in materials and (bio)materials science. We have successfully utilized a bioorganic approach to incorporate unnatural amino acids into the major sheath protein of M13 and, in one example, displayed > 350 azide moieties on the M13 surface which were further chemically modified to controllably attach fluorescent dyes and gold nanoparticles. Research to explore the additional capabilities of this engineered bacteriophage will be continued. For example, the ability to place recognition peptides onto the “ends” of these bacteriophage scaffolds and to furthermore crosslink them into larger complexes, should allow for the molecular delivery and/or targeting of these megabiocomplexes to a variety of materials and surfaces.**