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⁺.