This thesis includes two projects: "Novel perfluorinated aromatic amino acids: synthesis and applications" and "Thioflavin T dimers as novel amyloid ligands". I) Novel perfluorinated aromatic amino acids: synthesis and applications. Fluorinated amino acids serve as powerful tools in protein chemistry. Using the commercially available Boc-protected pentafluorophenylalanine, we synthesized a series of para-substituted tetrafluorophenylalanines via the regioselective SNAr reaction. These novel unnatural amino acids display useful and unique properties that can be applied to biological systems, including distinct 19F NMR signatures, pH-dependent amphiphilicity, lipid-binding selectivities, and halogen bonding capabilities. II) Thioflavin T dimers as novel amyloid ligands. Fluorescent molecules that specifically target amyloid structures are highly desirable for Alzheimer's disease research. We have designed a dimeric Thioflavin T that, through a reduced entropic penalty, has an improved binding affinity to Aβ amyloid by up to 70 fold. More importantly, the specificity and the "light-up" feature upon amyloid binding have not been sacrificed. Encouraged by the successful dimer design, we are further investigating the potential of amyloid-templated reactions to tailor-make ligands for amyloids.
