First rigid peptide foldamers with an alternating cis-trans amide sequence. An oligomeric building block for the construction of new helices, large-ring cyclic correlates, and nanotubes

As part of a program evaluating homochiral and heterochiral amino- and carboxylic acid-substituted gamma -lactams as conformationally constrained dipeptide building blocks, we have synthesized by the solid-phase technique and assessed by X-ray diffraction the crystal-state structure of the terminally blocked homotrimer from (2S,4R)-4-amino-5-oxopyrrolidine-2-carboxylic acid, characterized by a unique, alternating cis-trans amide sequence. Using computer modeling, we also showed that the rigid conformation of the trimer can be exploited as a template to construct novel linear oligopeptide foldamers and large-ring cyclic correlates with self-recognizing properties.