SEQUENCE-DEPENDENT REACTIVITY OF HISTIDINE-CONTAINING PEPTIDES WITH COPPER(II) ASCORBATE

Copper(II)/ascorbate-mediated oxidative damage to the peptide Asp-Arg-Val-Tyr-Ile-His-Pro-Phe was accompanied by the loss of Asp (64%), Arg (49%), Val (35%), and His (52%). In addition, the reaction of copper(II)/ascorbate with the peptide gave three products (AII-1, AII-2, and AII-3). AII-1 was confirmed to be the product of oxidized His, which generated the 2-imidazolone structure. The damage of the N-terminal sequence was reflected by AII-2 and AII-3. Hence, we characterized the reactivity of the N-terminal sequence using Asp-Arg, Arg-Val, Val-Tyr, and Asp-Arg-Val-Tyr. The reactivities of preferred sequences were Asp-Arg-Val-Tyr > Asp-Arg > Arg-Val > Val-Tyr, suggesting that the Asp-Arg-Val-Tyr sequence is important for the reactivity with Cu(II)/ascorbate. On the other hand, the peptide Ile-His-Pro-Phe, corresponding to the C terminus of the native peptide, failed to react with Cu(II)/ascorbate, suggesting that the Asp-Arg-Val-Tyr sequence contributes to the reactivity of His with copper(II)/ascorbate.