Conformational Analysis of Helical Peptides Incorporating Azepane-Based β-Amino Acids Prepared by an Ultrasound-Assisted Method

Abstract

We report the synthesis of cis-5-aminoazepane-4-carboxylic acid (cis-AAzC) and its conformational behavior in nontraditional helical peptides. An ultrasound-assisted reductive amination method improves chemical yields and reduces solvent usage compared with previous methods. Incorporation of cis-AAzC into unnatural peptides promotes the 11/9-helix in 1:1 α/β-peptides and the 12/10-helix in β-peptides with enhanced aqueous solubility. The circular dichroism and the crystal structure data for these peptides suggest that additional functionalization at the azepane moiety is tolerated without disrupting helical propensity.