Helical Foldamers Incorporating Photoswitchable Residues for Light-Mediated Modulation of Conformational Preference

An E unsaturated fumaramide linkage may be introduced
into Aib peptide foldamer structures by standard coupling methods
and photoisomerized to its Z (maleamide) isomer by
irradiation with UV light. As a result of the photoisomerization,
a new hydrogen-bonded contact becomes possible between the peptide
domains located on either side of the unsaturated linkage. Using the
fumaramide/maleamide linker to couple a chiral and an achiral fragment
allows the change in hydrogen bond network to communicate a conformational
preference, inducing a screw sense preference in the achiral domain
of the maleamide-linked foldamers that is absent from the fumaramides.
Evidence for the induced screw sense preference is provided by NMR
and CD, and also by the turning on by light of the diastereoselectivity
of a peptide chain extension reaction. The fumaramide/maleamide linker
thus acts as a “conformational photodiode” that conducts
stereochemical information as a result of irradiation by UV light.