No abstract

Fluorinated peptidomimetic foldamers are still in their infancy. We report here the easy access to fluorinated triazolamers based on 2-amino-3,3,3-trifluoropropyl-1,4-triazolyl acetic acid (CF 3 À 1,4-Tz) and on aminomethyl-1,4-triazolyl-difluoroacetic acid (1,4-TzÀ CF 2). Both CF 3 À 1,4-Tz and 1,4-TzÀ CF 2 amino acids were efficiently prepared by copper(I)-catalyzed Huisgen 1,3dipolar cycloaddition. Their conformational preferences were studied by 2D NMR analyses and molecular dynamic simulations. Foldamers based on CF 3 À 1,4-Tz amino acids are capable of adopting short multi-stranded β-sheet-like structures that are maintained by electrostatic interactions between the triazole proton and N2 atom of neighboring subunits. On the contrary, foldamers based on 1,4-TzÀ CF 2 units adopt elongated β-strandlike structures, stabilized by electrostatic interaction between fluorine atoms and their neighboring protons.