New Morphiceptin Peptidomimetic Incorporating (1 S ,2 R ,3 S ,4 S ,5 R )-2-Amino-3,4,5-trihydroxycyclopen-tane-1-carboxylic acid: Synthesis and Structural Study

We present the synthesis and structural study of a new peptidomimetic of morphiceptin, which can formally be considered as the result of the replacement of the central proline residue of this natural analgesic drug with a subunit of (1 ,2 ,3 ,4 ,5 )-2-amino-3,4,5-trihydroxycyclopentane-1-carboxylic acid, previously obtained from -idose. An optimized synthesis of this trihydroxylated cispentacin derivative is also reported. Molecular docking calculations on the target receptor support a favorable role of the hydroxy substituents of the non-natural β-amino acid incorporated into the peptidomimetic.