o-naphthalenedicarboxaldehyde derivative of 7′-aminonaltrindole as a selective δ-opioid receptor affinity label

Incorporation of a naphthalene-dialdehyde moiety into the δ antagonist, 6′-aminonaltrindole afforded a potent, selective, irreversible δ-agonist 1. However, flow cytometry studies revealed no time-dependent specific fluorescence, suggesting that both Lys214 and Cys216 at the recognition site are not involved in covalent binding. Molecular simulation studies suggest that compound 1 may form a Schiff base with the ε-amino group of Lys214, which could explain its irreversibility and transformation into a δ-agonist through a conformational change of TM5.