Folding is one of the most important processes in nature and provide the foundation for life. The amazing diversity of functions displayed by biomolecules is accessible with only 20 amino acids. It is inconceivable which functions are attainable by the innumerable available non-natural monomers. Therefore foldamers, non-natural folded oligomers, have aroused immense scientific interest. Here we show the synthesis and structural analysis of the first imidazole-pseudopeptide-based foldamer. The screw sense of the helix is determined by a single chiral imidazole unit which is attached at the N terminus of the oligomer. Circular dichroism (CD) spectroscopic investigations showed that the folding process depends on the water content of the solvent in a unique parabolic way. In a pure organic solvent, the helix is stabilized by hydrogen bonds between the amide hydrogen atoms and the nitrogen atoms of the azole ring. In aqueous solution, the folding process is driven by dispersion interactions. Surprisingly the formation of the helix is more pronounced in aqueous solution than in organic solvents. Furthermore, the helical structure can be switched from the folded to the unfolded structure by varying the temperature or by addition of copper(II)triflate or cyclam, respectively.

Imidazole-peptide foldamers: Switching of the driving forces within the helix

252nd National Meeting (2016)

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