Synthesis and structural characterization of helix-forming beta-peptides: trans-2-aminocyclopentanecarboxylic acid oligomers

Synthetic protocols and circular dichroism (CD) spectra are reported for a series of oligomers of (R,R)-trans-2-aminocyclopentanecarboxylic acid (tran s-ACPC). The two longest oligomers, a hexamer and an octamer, have also bee n examined crystallographically. Both crystal structures shaw that the beta -peptide backbone adopts a regular helix that is defined by a series of int erwoven 12-membered ring hydrogen bonds ("12-helix"). Each hydrogen bond li nks a carbonyl oxygen to an amide proton three residues toward the C-termin us. CD data suggest that the conformational preference of trans-ACPC oligom ers in methanol is strongly length-dependent, which implies that 12-helix f ormation is a cooperative process, as seen for the alpha-helix formed by co nventional peptides. Previous work has established that oligomers and polym ers of beta-amino acids can adopt helical conformations, but the 12-helix i s an unprecedented beta-peptide secondary structure.