Synthesis and Conformational Studies of Peptidomimetics Containing a New Bifunctional Diketopiperazine Scaffold Acting as a β-Hairpin Inducer

A practical synthesis of a new bifunctional diketopiperazine (DKP) scaffold 1, formally derived from
the cyclization of l-aspartic acid and (S)-2,3-diaminopropionic acid, is reported. DKP-1 bears a carboxylic
acid and an amino functionalities in a cis relationship, which have been used to grow peptide sequences.
Tetra-, penta-, and hexapeptidomimetic sequences were prepared by solution-phase peptide synthesis
(Boc strategy). Conformational analysis of these derivatives was carried out by a combination of 1H
NMR spectroscopy, IR spectroscopy, CD spectroscopy, and computer modeling, and reveals the formation
of β-hairpin mimics involving 10-membered and 18-membered H-bonded rings and a reverse turn of the
growing peptide chain.