Conformationally Constrained Mono-Fluorinated Arginine as a Cationic Label for Solid-State ¹⁹F NMR Analysis of Membrane-Bound Peptide

A conformationally constrained mono‐fluorinated analogue of arginine, (1S,3S)‐1‐amino‐3‐fluoro‐3‐(guanidinomethyl)cyclobutane‐1‐carboxylic acid (F‐CbArg), has been designed as a label for solid‐state ¹⁹F NMR spectroscopy. The compound was synthesized and its structural and functional similarity to arginine demonstrated in the context of a representative antimicrobial peptide. The cationic ¹⁹F NMR label was incorporated into the amphiphilic helix of temporin A and provided information on water and phosphate contacts within the lipid environment, thereby demonstrating the utility of F‐CbArg in structural studies of membrane‐bound peptides.