Evaluation of a Cyclopentane-Based γ‑Amino Acid for the Ability to Promote α/γ-Peptide Secondary Structure

We report the asymmetric synthesis
of the γ-amino acid (1R,2R)-2-aminomethyl-1-cyclopentane carboxylic
acid (AMCP) and an evaluation of this residue’s potential to
promote secondary structure in α/γ-peptides. Simulated
annealing calculations using NMR-derived distance restraints obtained
for α/γ-peptides in chloroform reveal that AMCP-containing
oligomers are conformationally flexible. However, additional evidence
suggests that an internally hydrogen-bonded helical conformation is
partially populated in solution. From these data, we propose characteristic
NOE patterns for the formation of the α/γ-peptide 12/10-helix
and discuss the apparent conformational frustration of AMCP-containing
oligomers.