Application of the rule of shielding in the design of novel fluorinated structural motifs and peptidomimetics

► Three bioisosteric fragments with deshielded fluorines have been compared and analyzed in the interactions with α helices. ► The rule of shielding has been applied to the design of novel peptidomimetics containing shielded fluorine atoms. ► The phi-psi conformational space of these fluorinated peptidomimetics has been analyzed and compared to other peptides.