Exploring the Conformation of Mixed Cis- Trans α,β-Oligopeptoids: A Joint Experimental and Computational Study.

The synthesis and conformational preferences of a set of new synthetic foldamers that combine both the alpha,beta-peptoid backbone and side chains that alternately promote cis- and trans-amide bond geometries have been achieved and addressed jointly by experiment and molecular modeling. Four sequence patterns were thus designed and referred to as cis-beta-trans-alpha, cis-alpha-trans-beta, trans-beta-cis-alpha, and trans-alpha-cis-beta. alpha- and beta NtBu monomers were used to enforce cis-amide bond geometries and alpha- and beta NPh monomers to promote trans-amides. NOESY and molecular modeling reveal that the trans-alpha-cis-beta and cis-beta-trans-alpha tetramers show a similar pattern of intramolecular weak interactions. The same holds for the cis-alpha-trans-beta and trans-beta-cis-alpha tetramers, but the interactions are different in nature than those identified in the trans-acis-beta-based oligomers. Interestingly, the trans-alpha-cis-beta peptoid architecture allows establishment of a larger amount of structure-stabilizing intramolecular interactions.