Structural characterization of peptide oligomers containing (1R,2S)-2-aminocyclohexanecarboxylic acid (cis-ACHC)

Abstract

(1R,2S)-2-Aminocyclohexanecarboxylic acid (cis-ACHC) is a preorganized β-amino acid. cis-ACHC favors two conformations that feature gauche conformations about the Cα-Cβ bond with torsion angles of opposite signs. The diastereomeric β-amino acid trans-ACHC has been widely studied as a foldamer building block, but cis-ACHC has received less attention in this regard. We examined the conformational behaviour of three types of oligomer: (1) homooligomers of cis-ACHC, (2) β-peptides in which cis-ACHC and β3h-Ala alternate, and (3) 1:1 α/β- peptides in which cis-ACHC and Ala alternate. Two-dimensional NMR experiments suggest that all three types of oligomer adopt extended conformations rather than folded conformations in solution. Two crystal structures of oligomers that contain cis-ACHC residues, a cis-ACHC dimer and an α/β-peptide tetramer, show extended conformations in which the cis-ACHC residues contain six-membered-ring C=O⋯H-N hydrogen bonds. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.