Fragmentation of Arginine- and Lysine-Containing Dipeptides Cationized by Cu + and Cu 2+

Using electrospray ionization mass spectrometry and plasma desorption mass spectrometry, the fragmentations of arginine, lysine and five arginine- or lysine-containing dipeptides (noted M) were examined when cationized by Cu⁺ and Cu²⁺. Fragmentations of the two basic amino acids showed that the MCu(I)⁺ complexes mainly lose 46 u ([2H, C, 2O]), while [M – H + Cu(II)]⁺ complexes are decarboxylated or lose 45 u. As a result, collision-induced dissociation mass spectra of both Cu(I) and Cu(II) complexes showed the same characteristic fragment: a cationized imine, noted [I – H + Cu], where I stands for the characteristic immonium ion usual in the fragmentation of non-basic protonated amino acids. Loss of 45 u from the [M – H + Cu(II)]⁺ion was attributed to the loss of an HO₂C^• radical. This might happen from an isomer in which the amino group is deprotonated, rather than the carboxylic group. Hydrogen migrations are, indeed, known to be facilitated by the coordination of copper. Fragmentations of the dipeptides showed that the sites of cleavage were the same in the MCu(I)⁺ and [M – H + Cu(II)]⁺ complexes and were directed by the position of the basic residue in the peptidic chain. Dipeptides with the basic residue at the C-terminus were decarboxylated, while dipeptides with the arginine or lysine at the N-terminus fragmented by losing the entire C-terminal residue. Mechanisms involving multidentate binding of the dipeptides with preferred coordination on the basic side chain and the N-terminal amino group are proposed as interpretation.