title: Influence of N-terminal acetylation and C-terminal proteolysis on the analgesic activity of beta-endorphin.
abstract: Removal of one, two and four amino-acid residues from the C-terminus of beta-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 beta-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 beta-endorphin is therefore necessary for the production of analgesia, whereas the C-terminal residues confer potency. The N alpha-acetyl form of beta-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 alpha-acetyl derivative of beta-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 of the N-terminus of beta-endorphin may constitute physiological mechanisms for inactivation of this potent analgesic peptide.
mesh_terms: D000107:Acetylation; D000700:Analgesics; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D004723:Endorphins / Q000494:pharmacology*; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D011957:Receptors, Opioid / Q000187:drug effects; D013329:Structure-Activity Relationship; D013997:Time Factors
chemical_list: D000700:Analgesics; D004723:Endorphins; D010446:Peptide Fragments; D011957:Receptors, Opioid