Fluorine-containing macrocyclic peptides and peptidomimetics

Abstract

Fluorination plays a vital role in medicinal chemistry due to the unique properties of the fluorine atom. Macrocyclic peptides offer advantageous properties compared to linear peptides in drug discovery. In recent years, the development of fluorinated macrocyclic peptides and peptidomimetics, such as voxilaprevir, MK-0616 and ulimorelin, has highlighted the growing interest in the combination of fluorination and cyclization for tuning the properties of peptidic drug leads. In this review, the effects of fluorination on biological properties of macrocyclic peptides will be discussed. The use of the fluorine atom as a ¹⁹F NMR spectroscopy probe for conformational studies of macrocyclic peptides will be reviewed. Finally, macrocyclic peptides containing the radionucleotide ¹⁸F as PET imaging agents will be highlighted.