Chapter 4 - Fluorinated Amino Acids, Peptides, and Proteins

Abstract

Diverse range of proteins with unique chemical and biological properties can be designed through site-directed or random mutagenesis using fluorinated amino acids of either stereochemical configuration, whereas relatively small peptides can be synthesized through solid-phase peptide synthesis. Even a single substitution of fluorinated amino acids into proteins may exert a dramatic effect on proteolytic and thermal stabilities of peptides and proteins. Synthetic fluorinated collagen-like peptides, incorporating 4-fluoroproline residues, bind tightly with mammalian collagen, and thus fluorinated-collagen-based biomaterials are potentially useful in skin grafting and restorative procedures. Fluorinated analogs of glucagon-like peptide (GLP)-1, with optimal binding affinity to GLP-1 receptor (GLP-1R) and with improved hydrolytic stabilities, are potential therapeutics in treating diabetes. Fluorinated versions of amino acids, especially those of leucine, tryptophan, phenylalanine, and tyrosine, are widely used to study protein folding and enzyme–substrate complexes. Global substitution of the amino acids in proteins by fluorinated amino acids often retains the biological activity of the wild-type proteins. This chapter outlines the applications of fluorinated amino acids in protein engineering for devising noncanonical peptides and proteins with enhanced thermal and proteolytic stabilities and with unique biological properties.