Design, Synthesis, and Application of an Optimized Monofluorinated Aliphatic Label for Peptide Studies by Solid-State 19F NMR Spectroscopy

A conformationally restricted monofluorinated alpha-amino acid, (3-fluorobicyclo[1.1.1]pentyl) glycine (F-Bpg), was designed as a label for the structural analysis of membrane-bound peptides by solid-state F-19 NMR spectroscopy. The compound was synthesized and validated as a F-19 label for replacing natural aliphatic alpha-amino acids. Calculations suggested that F-Bpg is similar to Leu/Ile in terms of size and lipophilicity. The F-19 NMR label was incorporated into the membrane-active antimicrobial peptide PGLa and provided information on the structure of the peptide in a lipid bilayer.