Synthetic hosts as scaffolds for biomolecular recognition

Biomolecular interactions are responsible for controlling and directing all cellular events. Gaining an approximate understanding of how these interactions are regulated and conducted will allow us to design synthetic moieties capable of imitating and interacting with central biological components. Creation of molecules with synthetic accessibility and stability in vivo furthers the potential inroads that scientists can make in elucidating these systems as well as controlling and preventing disease states. Model systems provide insight into the specific intermolecular interactions responsible for the myriad of molecular pairings observed in vivo . Specifically, we have used the N(10)-substituted flavin cofactor as a biologically relevant guest to dissect the relative importance of non-covalent interactions in enzymatic function. Information gained in these, and related experiments, can be used to further construct scaffolds capable of well-controlled interactions with larger targets. To expand on the insight gained from small model systems, we have developed a series of mixed monolayer protected gold clusters (MMPCs) to bind larger biomolecular targets. These gold nanoparticles have been studied both theoretically and in materials applications, but have not been used extensively for biological studies. Cationically-functionalized nanoparticles are observed to bind DNA. Characterization of the mechanistic features of this interaction is presented. The nanoparticles have also been utilized in transfection experiments, and proven to be effective vectors for introduction of a DNA plasmid into mammalian cells. Studies were completed to understand the mechanism by which the nanoparticles are incorporated into the cells, and to determine whether, and how, the nanoparticles may contribute to toxicity observed in transfection. Gold nanoparticles are only beginning to be studied for use in biological systems; it is the hope that the results herein will further the development of these versatile hosts as biomolecular effectors