Synthesis of the Prototypical Cyclopropyl Dipeptide Mimic and Evaluation of Its Turn-Inducing Capability.

The (+) and (-) enantiomers of a new turn-inducing cyclopropyl dipeptide mimic have been synthesized and evaluated. The mimic derives its turn-inducing capabilities solely from the cyclopropyl group and without the conformational biasing that would be provided by side-chain substituents. The mimic and peptide-mimic hybrids prepared from it have been studied using a combination of spectroscopic techniques (NMR, IR, and CD). The dipeptide mimic itself displays intramolecular hydrogen bonding in organic solvents, which differs from that observed in natural peptide turns. In contrast, more elaborate peptide-mimic hybrids exhibit hydrogen bonding characteristics that vary with solvent but are consistent with structures found in the tetrapeptide portion (i → i + 3) of a native ß-turn.

ß-Turn Mimics by Chemical Ligation.

We report a simple reductive amination protocol to ligate two peptides, while simultaneously installing a ß-turn mimic at the ligation junction. This strategy uses commercially available materials, mild chemical conditions, and a chemoselective ligation reaction of unprotected peptide substrates accessed through standard solid phase methods. This system was implemented in a designed ß-hairpin system, and biophysical analysis demonstrates effective mimicry of the ß-turn.