Monofluoroalkene-Isostere as a 19 F NMR Label for the Peptide Backbone: Synthesis and Evaluation in Membrane-Bound PGLa and (KIGAKI)3

Abstract

Solid-state ¹⁹ F NMR is a powerful method to study the interactions of biologically active peptides with membranes. So far, in labelled peptides, the ¹⁹ F-reporter group has always been installed on the side chain of an amino acid. Given the fact that monofluoroalkenes are non-hydrolyzable peptide bond mimics, we have synthesized a monofluoroalkene-based dipeptide isostere, Val-Ψ[(Z)-CF=CH]-Gly, and inserted it in the sequence of two well-studied antimicrobial peptides: PGLa and (KIGAKI)₃ are representatives of an α-helix and a β-sheet. The conformations and biological activities of these labeled peptides were studied to assess the suitability of monofluoroalkenes for ¹⁹ F NMR structure analysis.

Keywords: 19F-labeled peptides; circular dichroism; monofluoroalkene; solid state 19F NMR; vesicle leakage.