Oligomers of β-amino acid bearing non-planar amides form ordered structures

Abstract

In this report, we explore the feasibility of using bicyclic chiral β-amino acids, (1 R,2 R,4 S)- and (1 S,2 S,4 R)-7-azabicyclo[2.2.1]heptane-2-carboxylic acid ( R- Ah2c and S- Ah2c, respectively), to prepare novel peptides with unique properties. Facile cis–trans isomerization of the non-planar amide bonds of these β-amino acids should result in great flexibility of the backbone structure of β-peptides containing them. Indeed, oligomers of these amino acids showed thermostability and characteristic CD absorptions, which were not concentration-dependent, suggesting that the oligomers remained monomeric. The results indicated the formation of self-organized monomeric structures with chain-length-dependent stabilization. Energy calculations suggested that the peptides can take helical structures in which the energy barriers to cis–trans isomerization are greater for the central amide bonds than for the terminal amides.