Synthesis and conformational studies of a stable peptidomimetic β-hairpin based on a bifunctional diketopiperazine turn inducer

The design, synthesis and conformational studies of a new β-hairpin mimic, 2, are described in this paper. The design towards hairpin 2 is based on the assembly of the bifunctional DKP-1 as a β-turn inducer, a peptidomimetic strand, namely 5-amino-2-methoxybenzhydrazide, to stabilize the formation of β-sheets, and finally a tetrapeptide sequence, GVVI, containing the hydrophobic residues Val, Ile and Gly. The synthesis of hairpin 2 was performed in solution while the formation of the β-hairpin in protic solvents was proven by NMR investigations (1H and 13C chemical shifts, vicinal coupling constants and ROEs) and corroborated by computational studies (Monte-Carlo conformational search, molecular dynamics and DFT calculations). © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique.2015