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New Synthetic Methods for Integrating Metal Nanoparticles with Biomolecules

Abstract

Integrated systems that incorporate biomolecules, organic small molecules, and inorganic materials with precise, nanoscale positional relationships present a great synthetic challenge yet to be mastered by `top down' engineering approaches or `bottom up' chemical synthetic methods. Focusing on this challenge, we have developed well defined protein-inorganic nanomaterial conjugates to understand fundamental photophysical properties and develop new materials for targeted dual fluorescence/electron microscopy. First, we designed and constructed three systems to explore the effect of metal nanoparticles on organic fluorophores. The basis of these systems was the spherical protein capsid of bacteriophage MS2, which was used to house either organic fluorophores or gold particles within its interior volume. The exterior surface of each capsid was modified with ssDNA to facilitate the placement of either a gold nanoparticle or a fluorophore of interest at a fixed distance from the capsid. Next, pairing reported external modification strategies for MS2 that target both native and unnatural amino acids with a variety of interior inorganic cargo, we sought to produce additional materials for metal controlled fluorescence (silver nanoparticles), dual fluorescence/electron microscopy (CdSe/ZnS quantum dots and CdSe/CdS dot rods), and electron microscopy (discrete gold nanoparticle assemblies). Finally, a previously reported oxidative coupling reaction between anilines and ortho-aminophenols was adapted for gold nanoparticle bioconjugation. The reaction proceeds under mild conditions with fast reaction times and little-to-no background protein adsorption to the gold nanoparticles.

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