Influence of N-terminal acetylation and C-terminal proteolysis on the analgesic activity of β-endorphin

Abstract

Removal of one, two and four amino-acid residues from the C-terminus of β-endorphin ('lipotropin C-Fragment', lipotropin residues 61-91) led to the formation of peptides with progressively decreased analgesic potency; there was no change in the persistence of the analgesic effects. The four C-terminal residues are thus important for the activity of β-endorphin, but not for the duration of action. Removal of eight amino-acid residues from the N-terminus provided a peptide that had no specific affinity for brain opiate receptors in vitro and was devoid of analgesic properties. The N-terminal sequence of β-endorphin is therefore necessary for the production of analgesia, whereas the C-terminal residues confer potency. The N(α)-acetyl form of β-endorphin had no specific affinity for brain opiate receptors in vitro and possessed no significant analgesic properties. Since lipotropin C'-Fragment (lipotropin residues 61-87) and the N(α)-acetyl derivative of β-endorphin occur naturally in brain and pituitary and are only weakly active or inactive as opiates, it is suggested that proteolysis at the C-terminus and acetylation at the N-terminus of β-endorphin may constitute physiological mechanisms for inactivation of this potent analgesic peptide.