Harnessing the Power of Fluorination for Protein Engineering

Thesis advisor: Jianmin GaoA common method of studying proteins is to introduce mutations into the amino acid sequence of the system. Incorporating phenylalanine analogs of varying degrees and sites of fluorination on the aromatic system gave substantial insight into the structure—function relationship of model peptide systems. By strategically placing tetrafluorinated phenylalanine mutants into the villin headpiece, HP35, increased thermodynamic and thermal stability was achieved. Using these highly but not fully fluorinated novel amino acid analogs allowed for the retention of the important ArH•••π interactions of the system. Furthermore, fluorinated amino acid residues were introduced into peptide systems known to form pores in lipid membrane systems. Certain fluorinated mutants of the membrane pore-forming peptides (MPP) showed increased membrane activity. Thus, fluorinated amino acids have tremendous potential to create hyperstable protein conformations, as well as increase the activity of proteins in membranes.Thesis (BS) — Boston College, 2009.Submitted to: Boston College. College of Arts and Sciences.Discipline: College Honors Program.Discipline: Chemistry