Phosphorus-based reagents in peptide synthesis: synthesis of methionine-enkephalin and the solution conformation of its N-diphenylphosphinoyl derivative

Abstract

Met5enkephalin 1 was synthesized by solution phase synthesis using the diphenylphosphinoyl (Dpp) group for α-amino group protection and diphenylphosphinoyl–carboxylic acid mixed anhydrides for carboxylate activation. These reagents proved to be compatible with both tyrosine and methionine side chain functionalities. A 1H NMR study of the solution conformation of the N-terminal-protected pentapeptide DppMet5enkephalin 2 in [2H6]dimethyl sulfoxide suggests that the peptide backbone of this derivative adopts a major conformation possessing a type I′β-bend between residues Gly2–Gly3 with the side chains of the Tyr1 and Phe4 lying on the same side of the plane of the bend. The predominant conformations of the Phe4 and Met5 side chains appear to be tg+.