An N-ortho-nitrobenzylated benzanilide amino acid enables control of the conformation and membrane permeability of cyclic peptides.

We designed and synthesized an N-ortho-nitrobenzylated benzanilide-based amino acid having a cis-amide structure that facilitates cyclization of peptides containing it. Photo-induced removal of the nitrobenzyl group from this residue in the resulting cyclized peptides dramatically alters their conformation and passive membrane permeability via complete cis-amide to trans-amide conversion.