The recently discovered native endomorphin 2 plays an important role in opioid analgesia, but its metabolic fate in the organism remains relatively little known. The successful synthesis of endomorphin 2 was carried out by solution method. The C teminal dipeptide and the N terminal dipeptide have been synthesized, respectively, and then coupled successfully. High performance liquid chromatography and electrospray ionization mass spectrometry were used to identify the degradation products from the incubation of endomorphin 2 with brain synaptic membrane. The patterns of peptide metabolites indicated that brain synaptic membrane associated peptidases hydrolyzed first at the N terminal, and then split the peptide at the Phe Phe bond.
