(I) Novel Perfluorinated Aromatic Amino Acids: Synthesis and Applications (II) Thioflavin T Dimers as Novel Amyloid Ligands

Thesis advisor: Jianmin GaoThesis advisor: James P. MorkenThis 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.Thesis (PhD) — Boston College, 2012.Submitted to: Boston College. Graduate School of Arts and Sciences.Discipline: Chemistry

Synthesis of Tetrafluorinated Aromatic Amino Acids with Distinct Signatures in ¹⁹F NMR

Fluorinated amino acids serve as powerful tools in protein chemistry. We synthesized a series of <i>para</i>-substituted tetrafluorophenylalanines via the regioselective S_NAr chemistry of the commercially available pentafluorophenylalanine Boc-Z. These novel unnatural amino acids display distinct ¹⁹F NMR signatures, making them powerful tools for analyzing protein–membrane interactions with NMR spectroscopy