Proton magnetic resonance studies of conformation and flexibility of enkephalin peptides

Proton magnetic resonance (PMR) studies of Met5-enkephalin 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-Phe as proposed previously6.

Abstract

ENKEPHALIN, an endogenous pentapeptide which has the analgesic properties of morphine1, has recently been isolated, purified and characterised both chemically and pharmacologically2,3. 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 features4,5. 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 oripavine4,5. 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.