From glucose to enantiopure morpholino β-amino acid: a new tool for stabilizing γ-turns in peptides

A new cyclic enantiopure b-amino acid, named b-Morph, containing the morpholino ring, was obtained in gram scale starting from alfa-D-glucopyranose enantiopure material, focusing on the “environmental sustainability” concept. A series of ultrashort model peptides containing b-Morph were prepared. b-Morph was found able to induce an inverse gamma-turn in Leu-Val containing sequences. Key element for the gamma-turn formation might be the oxygen atom of morpholino ring that could drive the spatial orientation of NH of amino acid i+1, through an unusual hydrogen bond. This datum was confirmed by QTAIM calculations. Interestingly, when two b-Morph-Leu-Val repeats are present in the peptide, two gamma-turns can be formed, as supported by NMR experiments and aMD and H-REMD calculations.