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

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