| Summary: | The advent of nanobiotechnology has accelerated the application of nanoparticle in biological systems. The unique chemical and physical properties of nanoparticles have established their utility in the sensing and visualization of biological processes. Our goal, however, was to use nanoparticles to control biological activities, specifically through binding protein surfaces. Protein surface binding provides a powerful tool for evaluating and controlling biological processes beyond the scope of small molecules. Monolayer protected nanoparticles are versatile macromolcular scaffolds for protein surface binding. We have demonstrated the use of nanoparticles for efficient binding and inhibition of a model enzyme, chymotrypsin. Nanoparticles featuring a carboxylate-terminated alkanethiol monolayer elicited inhibition by a two-step process; initial binding via electrostatic complementarity followed by slow denaturation. By integrating poly(ethylene glycol) between the recognition unit and the alkane monolayer, inhibition was achieved with no change in chymotrypsin conformation, demonstrating the ability to control the mechanism of enzyme inhibition. Further control of the inhibition can be mediated through modification of the nanoparticle monolayer using cationic surfactants. These strategies for protein surface binding using nanoparticles as a scaffold have been extended to a more complex protein system by decorating the nanoparticles with target-specific peptides. In this manner, the interaction between HDM2 and p53 was successfully disrupted.
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