Molecular Interactions of Fluorinated Amino Acids in a Native Polypeptide Environment

Publisher Summary This chapter investigates the effects of fluorinated amino acid substitutes on the interactions with natural protein environments. Amino acid side chain fluorination highly affects polypeptide folding due to steric effects, polarization, and fluorous interactions. Intermolecular interactions represent the main regulatory machinery of a wide variety of biological processes such as signal transduction, cell–cell communication, catalysis, as well as metabolism and hormone regulation. Peptides and proteins play a powerful role in these functions because of their structural and functional versatility. They can take part in various interactions of a hydrophobic as well as dipolar and ionic nature depending on the side chain functionalities of the amino acids within the sequence. Because of steric effects, the three-dimensional structure of a protein may also contribute to molecular recognition. Protein folding and activity are based on a multitude of molecular interactions. Single amino acid side chains modulate the nature and strength of such interactions. The metabolic and structural stability of peptides and proteins that contain fluorinated substituents have been studied extensively in recent years. However, the application of fluorinated building blocks to the de novo design of peptides and proteins requires a detailed knowledge of molecular interactions directed by the fluorine atom.