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

Abstract

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 (1S,2R,3S,4S,5R)-2-amino-3,4,5-trihydroxycyclopentane-1-carboxylic acid, previously obtained from L-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.

Keywords

• morphiceptin
• alicyclic β-amino acids
• peptidomimetics
• nitro sugars
• analgesic