Influence of degradation on binding properties and biological activity of endomorphin 1

The recently-isolated endogenous peptide endomorphin 1 has high affinity fo r the mu opioid receptor and plays an important role in analgesia. Several of its degradation products have been isolated from the central nervous sys tem, Degradation products present structural similarities and may influence the receptor binding properties and biological activity of the parent comp ound. Therefore, we investigated how degradation of endomorphin 1 might inf luence ligand binding to the mu opioid receptor, the consequent activation of G proteins and its antinociceptive effect. Both N- and C-terminal trunca tion of endomorphin 1 resulted in peptides presenting considerably lower op ioid receptor binding potency. None of these peptides had an effect on GTP binding, nor was able to produce analgesia, suggesting that degradation des troys the biological activity of endomorphin 1. (C) 2001 Academic Press.