Tinker, Tailor, Soldier, Spy: The Diverse Roles That Fluorine Can Play within Amino Acid Side Chains

Side chain-fluorinated amino acids are useful tools in medicinal chemistry and protein science. In this review, we outline some general strategies for incorporating fluorine atom(s) into amino acid side chains and for elaborating such building blocks into more complex fluorinated peptides and proteins. We then describe the diverse benefits that fluorine can offer when located within amino acid side chains, including enabling (19)F NMR and (18)F PET imaging applications, enhancing pharmacokinetic properties, controlling molecular conformation, and optimizing target-binding.