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 Pn (n = 2, 4, 8) were first synthesized but show no sign of folding in solution in organic solvents, unlike the Qn oligomers from which they are derived, which adopt particularly stable helical conformations. Hybrid oligomers (PQ)n (n = 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 Qn oligomers.