Novel amphiphilic alpha-helix mimetics based on a bis-benzamide scaffold.

ABSTRACT

To mimic amphiphilic alpha-helices, a new scaffold was designed based on a bis-benzamide that places four side-chain functional groups found at the i, i+2, i+5, and i+7 positions of a helix. Its two hydrogen bonds fix the conformation and provide accurate bifacial arrangement of the four substituents, simultaneously representing two opposing helical sides. An efficient synthetic route was achieved for the construction of bis-benzamides, and their superior alpha-helix mimicry was confirmed by X-ray crystallography.