The Herringbone Helix:  A Noncanonical Folding in Aromatic−Aliphatic Peptides

Hybrid oligomeric sequences derived from both aliphatic and aromatic units are shown to adopt a folded conformation with an unprecedented architecture. Specifically, a δ-amino acid bearing an aliphatic amine6-aminomethyl-2-pyridinecarboxylic (P)was designed and synthesized as a flexible analogue of 6-amino-2-quinolinecarboxylic acid (Q). Oligomers P<i><sub>n</sub></i> (<i>n</i> = 2, 4, 8) were first synthesized but show no sign of folding in solution in organic solvents, unlike the Q<i><sub>n</sub></i> oligomers from which they are derived, which adopt particularly stable helical conformations. Hybrid oligomers (PQ)<i><sub>n</sub></i> (<i>n</i> = 1, 2, 4) were also prepared and were shown to adopt a novel folded conformation in the solid state where PQ units arrange into two stacks at a 90° angle from each other. Comprehensive NMR studies demonstrate that in solution this peculiar organization coexists with a helical conformation resembling that of Q<i><sub>n</sub></i> oligomers.