Self-assembling proteins as templates for gold nanoparticle arrays

Nature has developed a highly evolved approach to forming macromolecular structures and complex three-dimensional systems through the assembly of molecular building blocks. Many proteins used for this purpose are readily available in abundance, and have been observed to assemble in vitro into complex structures that display periodic nanometer-sized features. A modular coupling strategy has been developed to allow for the site-selective modification of proteins with a variety of materials. Once conjugated to appropriately functionalized nanocrystals, modified proteins could be induced to assemble and arrange into arrays possessing both nanometer-scale organization and long range structure.; Chapter 1 outlines a modular coupling strategy for the synthesis of nanoscale materials using proteins as templates for nanoparticle arrays. Specifically, reactions leading to the formation of hydrazones and oximes are the focus, as these reactions can be readily performed under physiological conditions. Towards this strategy, three different preparations of functionalized gold nanoparticles ranging in size from 0.8--15 nm are described.; Chapter 2 illustrates the utility of our modular coupling strategy, as we use two viral capsids, tobacco mosaic virus (TMV) and bacteriophage MS2 as scaffolds for templating nanoparticle arrays. These scaffolds provide multiple surfaces to elaborate, thus giving rise to new core-shell materials combining inorganic nanoparticles with organic fluorophores. As nanoparticles come within close proximity of each other, plasmonic enhancements can be observed; however, incomplete coverage of the capsid surfaces led to the absence of these effects. Current efforts are focused on increasing labeling efficiencies.; Chapter 3 outlines our progress towards the preparation of actin as a linear template for nanoscale materials. Inherent ketone reactivity of unmodified actin impairs our ability to use our modular coupling strategy, however, we have found covalent modifications that allow for the functionalization of the actin monomer without inhibiting actin polymerization. Additionally, derivatives of cytochalasin B have been synthesized to facilitate end functionalization of assembled fibers.; Lastly, Chapter 4 describes our initial results in the development of a new carbon-carbon bond forming reaction on ketone-bearing peptides. An N-terminal thioester is installed as the product under aqueous conditions and with as little as 5 equivalents of small molecule relative to substrate. These new architectures can be used in protein synthesis to complement current native chemical ligation techniques.