Aromatic oligoesters as novel helix mimetic scaffolds.

The design, synthesis, and conformational analysis of a novel aromatic oligoester helix mimetic scaffold is reported. A range of amino acid-type side-chain functionality can be readily incorporated into monomer building blocks over three facile synthetic steps. Analysis of representative dimers revealed a stable conformer capable of effective mimicry of a canonical α-helix and the scaffold was found to be surprisingly stable to degradation in aqueous solutions at acidic and neutral pH.

Design, Synthesis, and Conformational Analysis of Oligobenzanilides as Multifacial α-Helix Mimetics.

The design, synthesis, and conformational analysis of an oligobenzanilide helix mimetic scaffold capable of simultaneous mimicry of two faces of an α-helix is reported. The synthetic methodology provides access to diverse monomer building blocks amenable to solid-phase assembly in just four synthetic steps. The conformational flexibility of model dimers was investigated using a combination of solid and solution state methodologies supplemented with DFT calculations. The lack of noncovalent constraints allows for significant conformational plasticity in the scaffold, thus permitting it to successfully mimic residues i, i+2, i+4, i+6, i+7, and i+9 of a canonical α-helix.