1448639-64-2Relevant articles and documents
Structural and biological exploration of Phe3-Phe 4-modified endomorphin-2 peptidomimetics
Lesma, Giordano,Salvadori, Severo,Airaghi, Francesco,Murray, Thomas F.,Recca, Teresa,Sacchetti, Alessandro,Balboni, Gianfranco,Silvani, Alessandra
supporting information, p. 795 - 799 (2013/09/02)
This study reports on our ongoing investigation on hybrid EM-2 analogues, in which the great potential of β-amino acids was exploited to generate multiple conformational modifications at the key positions 3 and 4 of the parent peptide. The effect on the opioid binding affinity was evaluated, by means of ligand stimulated binding assays, which indicated a high nanomolar affinity toward the μ-receptor, with appreciable μ/δ selectivity, for some of the new compounds. The three-dimensional properties of the high affinity μ opioid receptor (MOR) ligands were investigated by proton nuclear magnetic resonance, molecular dynamics, and docking studies. In solution, the structures showed extended conformations, which are in agreement with the commonly accepted pharmacophore model for EM-2. From docking studies on an active form of the MOR model, different ligand-receptor interactions have been identified, thus confirming the ability of active compounds to assume a biologically active conformation.
