15 - Synthesis of Side Chain Fluorinated Amino Acids and Their Effects on the Properties of Peptides and Proteins

Abstract

Fluorination is a useful tool in medicinal chemistry. It is also increasingly applied in the field of peptide and protein engineering to address its unique challenges. The development of synthetic approaches toward fluorinated analogs of aminobutyric acid, valine, leucine, and isoleucine, described herein, has enabled the rational design of fluorinated peptides and studies of their properties. Important factors that influence the formation of secondary structures in proteins are volume, shape (topology), hydrophobicity, propensity for secondary structures, and electronic characteristics of the amino acid side chains. In view of this, studies that include the effect of site-specific fluorination of peptides on all these properties are described. Additionally, our studies that involve effects of side chain fluorination on amyloid formation and protein–protein interactions within enzyme binding sites are discussed.