OPIOID PEPTIDES AND THEIR RELATIVES

The critical structure responsible for opiate peptide activity is Tyr-Gly-Gly-Phe-(X), where X is a hydrophobic amino acid such as methionine or leucine in Met and Leu-enkephalin. There is now overwhelming evidence that a family of related lipotropin/corticotropin intermediate lobe peptides are derived from a common glycoprotein precursor of molecular weight ~ 30,000. The existence of so many potentially active molecules in one precursor is a subject of much interest. The question of how pro-opiocortin cleavage is regulated is thus an intriguing and important one. Pro-opiocortin is a glycosylated peptide and glycosylation may be important for protection of the prohormone from nonspecific proteolysis during packaging and could also direct cleavage of specific sequences through conformational effects. A disturbance of glycosylation in pathological states could lead to the production of 'abnormal' neuropeptides with undesirable side-effects on neuronal function.