Proton magnetic resonance studies of conformation and flexibility of enkephalin peptides

Abstract

ENKEPHALIN, an endogenous pentapeptide which has the analgesic properties of morphine¹, has recently been isolated, purified and characterised both chemically and pharmacologically^2,3. The fact that enkephalin and the opiates interact with the same receptor raises the possibility that the similarity in their function might be based on common structural features^4,5. Particular attention has been paid to the geometric relationship between the aromatic ring of the tyrosine residue and the terminal amino group of enkephalin compared with the known geometry of similar functional groups in morphine. The relative spatial disposition of the phenylalanine and tyrosine aromatic side chains is also of special interest because of the possible resemblance of enkephalin to oripavine^4,5. So far, however, no experimental determination of conformational parameters has appeared. Here we report proton magnetic resonance (PMR) studies of Met⁵-enkephalin which indicate that the methionine amino proton is involved in a hydrogen bond, most probably within a Gly–Gly–Phe–Met type I β turn, but not with a turn involving Tyr–Gly–Gly–Phe as proposed previously⁶. Although our data exclude a γ turn, they do not rigorously exclude other conformations, especially if these have small statistical weights.