Conformation of Met⁵-enkephalin determined by high field PMR spectroscopy

Abstract

THE discovery by Hughes et al.¹ that peptides (the enkephalins) could be the endogenous agonists of opiates in brain represents a challenge to medical chemistry both in its fundamental aspects and for the possible development of new therapeutic approaches. To understand how non-peptidic substances belonging to various chemical classes can mimic the action of the pentapeptide enkephalins it is first necessary to determine the spatial arrangement of the latter. We have thus synthesised large quantities of Met⁵-enkephalin (H–Tyr–Gly–Gly–Phe–Met–OH) and determined its preferential conformation in solution using high field proton magnetic resonance (PMR) spectroscopy at variable temperatures, coupling constants in relation with Karplus–Bystrov curves² and conformational energy steric maps³.