The application of fluorinated α-amino acids to drug discovery techniques

INTRODUCTION: While fluorinated amino acids (FAAs) have been utilized for the discovery and development of both small molecules and therapeutic peptides, it is important to also recognize the stand-alone value of these entities. The ability of fluorine to replace hydrogen in naturally occurring amino acids (or indeed be incorporated in unnatural/novel amino acids) without a significant perturbation in the steric properties of the molecule allows direct substitutions to seamlessly occur, while the 'unique' nature of the fluorine atom itself allows these 'analogues' to be utilized in biological systems. AREAS COVERED: This review discusses several areas where fluorinated amino acids (FAAs) have been directly employed within drug discovery. While by no means comprehensive, the examples and case studies described are intended not only to demonstrate current applications but also to illustrate both the vast potential and the array of challenges that still arise in these areas. EXPERT OPINION: F-NMR with cryo-EM for fragment-based drug discovery, provide a compelling path for more efficient drug discovery.