Physical Sciences and Mathematics Commons^™

Development Of In Vivo Systems For Detecting And Studying Ribosome Inhibition By Small Molecules, Shijie Huang

Chemistry and Chemical Biology ETDs

The ribosome is the quintessential antibacterial drug target, with many structurally and mechanistically distinct classes of antibacterial agents acting by inhibiting ribosome function. Detecting and quantifying ribosome inhibition by small molecules and investigating their binding modes and mechanisms of action are critical to antibacterial drug discovery and development efforts. To develop a ribosome inhibition assay that is operationally simple, yet provides direct information on the drug target and the mechanism of action, we have developed engineered E. coli strains harboring an orthogonal ribosome controlled green fluorescent protein reporter that produce fluorescent signal when the O-ribosome is inhibited. As a proof …

Development And Application Of An Expanded Streptomyces Genetic Code, Jingxuan He

Chemistry and Chemical Biology ETDs

Actinobacteria, especially those of genus Streptomyces, are a prominent source of bioactive natural products. The ability to site-specifically incorporate unnatural amino acids (UAAs) into natural product biosynthetic enzymes and ribosomally derived peptides in these organisms would constitute a valuable tool for drug discovery and development. The work described in this dissertation focuses on development and application of an expanded Streptomyces genetic code, including development of UAA incorporation systems based on amber suppression and sense codon reassignment, structural diversification of the model thiopeptide natural product thiostrepton using UAAs, and mapping protein-protein interactions in type II polyketide biosynthetic enzymes using photocrosslinking …

Engineering Small Molecule Based Dimerization To Induce Translation And Provide Optogenetic Control, Catherine Wright

Chemistry and Chemical Biology ETDs

We wanted to develop a system that combines the spatial control of photoactivation and control of translation to build a tool to spatially control translation in neurons. This kind of tool could be used to investigate the role of spatially controlled translation of any protein in neural behavior. In this way the development and growth of neural processes could be studied to elucidate the mechanisms for spatially sensitive events such as pathfinding, repair, or long-term potentiation.

Chemically induced dimerization was used to install a switch into the activation of translation for specific genes. An abscisic acid (ABA) dependent dimerization of …

Molecular Tetrapods For Optoelectronic Applications, Jianzhong Yang

Chemistry and Chemical Biology ETDs

In this dissertation, several molecular tetrapods were synthesized for optoelectronic applications. In the first two sections, two tetrapodal breakwater-like small molecules: SO and SFBTD were synthesized and characterized. Absorption, X-ray scattering and differential scanning calorimetry experiments indicate crystalline nature of these compounds but slow crystallization kinetics. Solar cells employing SO or SFBTD and phenyl-C₆₁-butyric acid methyl ester (PCBM) were fabricated and evaluated. Relatively low performance was obtained mainly due to the lack of appropriate phase separation, which was caused by molecularly mixed blends with PCBM. The molecularly mixed blends is the result of slow crystallization …