Nickel-catalyzed N-terminal oxidative deamination in peptides containing histidine at position 2 coupled with sulfite oxidation

Peptides containing histidine at position 2 were observed to undergo sponta neous N-terminal oxidative deamination in aqueous solution in the presence of Ni(II), sulfite, and ambient oxygen. The reaction resulted in the format ion of a free carbonyl on the N-terminal alpha-carbon (alpha-ketoamide) and was catalytic with respect to nickel. This oxidative deamination was confi rmed by C-13 NMR, H-1 MMR, mass spectrometry, and chemical tests. No eviden ce of modification of histidine was found. It was demonstrated that the nic kel-dependent N-terminal oxidative deamination also occurred in His-2 pepti des using potassium peroxymonosulfate (oxone) as an oxidant. When oxone was used, oxygen was not required for the deamination to proceed. The results suggest that both nickel-catalyzed reactions (sulfite and oxygen, and oxone ) produce an imine intermediate that spontaneously hydrolyzes to form the f ree carbonyl, These findings may provide a physiologically relevant model f or oxidative carbonyl formation in vivo, as well as a useful method for pro ducing a site-specific carbonyl on peptides and proteins.