Comparison of the pH-dependent formation of His and Cys heptapeptide complexes of nickel(II), copper(II), and zinc(II) as determined by ion mobility-mass spectrometry.

The analog methanobactin (amb) peptide with the sequence ac-His1 -Cys2 -Gly3 -Pro4 -Tyr5 -His6 -Cys7 (amb5A ) will bind the metal ions of zinc, nickel, and copper. To further understand how amb5A binds these metals, we have undertaken a series of studies of structurally related heptapeptides where one or two of the potential His or Cys binding sites have been replaced by Gly, or the C-terminus has been blocked by amidation. The studies were designed to compare how these metals bind to these sequences in different pH solutions of pH 4.2 to 10 and utilized native electrospray ionization (ESI) with ion mobility-mass spectrometry (IM-MS) which allows for the quantitative analysis of the charged species produced during the reactions. The native ESI conditions were chosen to conserve as much of the solution-phase behavior of the amb peptides as possible and an analysis of how the IM-MS results compare with the expected solution-phase behavior is discussed. The oligopeptides studied here have applications for tag-based protein purification methods, as therapeutics for diseases caused by elevated metal ion levels or as inhibitors for metal-protein enzymes such as matrix metalloproteinases.