A Racemization-Free Coupling Method for Peptides Having N-Methylamino Acids at the Carboxy-Termini

Abstract

To search for recemization-free coupling conditions for peptides having N-alkylamino acids at the carboxy-termini, a model coupling using Boc-Phe-MeAla-OH (MeAla, N-methylalanine) and H-Phe-OBzl was studied. When benzotriazolyl-N-oxytris(dimethylamino)phosphonium hexafluorophosphate or O-(7-azabenzotriazol-1-yl)-1, 1, 3, 3, -tetramethyluronium hexafluorophosphate was employed as a coupling reagent, no additives so far examined could sufficiently suppress the racemization of the carboxy-terminal MeAla residue. Though N-hydroxy compounds were not satisfactorily effective also in 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (WSCI)-mediated coupling, CuCl₂ could eliminate the racemization of MeAla in the coupling with WSCI even at room temperature.