Antiparallel Self-Association of a γ,α-Hybrid Peptide: More Relevance of Weak Interactions

To learn how a preorganized peptide‐based molecular template, together with diverse weak non‐covalent interactions, leads to an effective self‐association, we investigated the conformational characteristics of a simple γ,α‐hybrid model peptide, Boc‐γ‐Abz‐Gly‐OMe. The single‐crystal X‐ray diffraction analysis revealed the existence of a fully extended β‐strand‐like structure stabilized by two non‐conventional C−H⋅⋅⋅O=C intramolecular H‐bonds. The 2D 1H NMR ROESY experiment led us to propose that the flat topology of the urethane‐γ‐Abz‐amide moiety is predominantly preserved in a non‐polar environment. The self‐association of the energetically more favorable antiparallel β‐strand‐mimic in solid‐state engenders an unusual ‘flight of stairs’ fabricated through face‐to‐face and edge‐to‐edge Ar⋅⋅⋅Ar interactions. In conjunction with FT‐IR spectroscopic analysis in chloroform, we highlight that conformationally semi‐rigid γ‐Abz foldamer in appositely designed peptides may encourage unusual β‐strand or β‐sheet‐like self‐association and supramolecular organization stabilized via weak attractive forces. The secret to getting organized: The crystallographic analysis of a non‐chiral γ,α‐hybrid model peptide Boc‐γ‐Abz‐Gly‐OMe revealed template‐assisted self‐association of monomeric flat β‐strand mimic. The urethane‐γ‐Abz‐amide foldamer self‐organized into an unusual ‘flight of stairs’ fabricated via face‐to‐face and edge‐to‐edge aromatic–aromatic interactions.