Synthesis and Structural Characterization of Helix-Forming β-Peptides:  <i>trans</i>-2-Aminocyclopentanecarboxylic Acid Oligomers

Abstract

Synthetic protocols and circular dichroism (CD) spectra are reported for a series of oligomers of ( R,R )- trans -2-aminocyclopentanecarboxylic acid ( trans -ACPC). The two longest oligomers, a hexamer and an octamer, have also been examined crystallographically. Both crystal structures show that the β-peptide backbone adopts a regular helix that is defined by a series of interwoven 12-membered ring hydrogen bonds (“12-helix”). Each hydrogen bond links a carbonyl oxygen to an amide proton three residues toward the C-terminus. CD data suggest that the conformational preference of trans -ACPC oligomers in methanol is strongly length-dependent, which implies that 12-helix formation is a cooperative process, as seen for the α-helix formed by conventional peptides. Previous work has established that oligomers and polymers of β-amino acids can adopt helical conformations, but the 12-helix is an unprecedented β-peptide secondary structure.