Application of the rule of shielding in the design of novel fluorinated molecules and peptidomimetics

The local environment around the fluorine, which determines the 19F chemical shift, appears to be of paramount importance for the recognition mechanism. Deshielded fluorinated fragments, suitable for interacting efficiently with the amphiphatic α helix secondary structural motif, are discussed. Shielded fluorinated scaffolds are proposed as novel peptide bond isosteres for potentially overcoming the major drawbacks of peptides, such as short physiological half-lives due to rapid proteolysis and poor bioavailability. These new fluorinated skeletons can be used for generating a diverse library of fluorinated peptide mimetics which can then be effectively screened in mixtures against multiple targets by 19F NMR spectroscopy