Identification of an electrostatic toolkit for encoding fluorinated phenylalanine residues within proteins expressed in prokaryotic and mammalian cells

Abstract

The aromatic side-chains of phenylalanine, tyrosine, and tryptophan engage in a variety of chemically expedient bonding modes. These interactions may range from purely hydrophobic/steric contributions to bona fide electrostatic bonds owing to the quadruple moment on the face of the aromatic. Explicitly testing the functional role for a given aromatic side chain is difficult using conventional mutagenesis, since mutation to a non-aromatic natural amino acid causes concomitant changes in amino acid shape, while obliterating the electrostatic component in an all-or-none manner.