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

International audienceThe design, synthesis and conformational studies of a new beta-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 beta-turn inducer, a peptidomimetic strand, namely 5-amino-2-methoxybenzhydrazide, to stabilize the formation of beta-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 beta-hairpin in protic solvents was proven by NMR investigations (H-1 and C-13 chemical shifts, vicinal coupling constants and ROEs) and corroborated by computational studies (Monte-Carlo conformational search, molecular dynamics and DFT calculations)