Biosynthetic origin and receptor conformation of methionine enkephalin

Abstract

RECENT reports have shown that the brain contains an endogenous peptide with opiate-like activity^1–3 and similar peptides have been found in the pituitary^4,5,13. One of the brain peptides, known as methionine enkephalin, was identified as a pentapeptide Tyr–Gly–Gly–Phe–Met⁶, and evidence was presented that a minor component may have leucine in place of methionine. The principal sequence is identical to that at the NH₂-terminus of lipotropin C fragment, a peptide discovered in substantial quantity in porcine pituitary^7,8. This suggests that methionine enkephalin is derived in vio by proteolytic cleavage of C fragment. Since enkephalin is thought to compete directly with opiates for the brain opiate receptor, while having no primary structure similarity to opiates, we have searched for and found a basis for the competition in a proposed secondary structure for the peptide.