Binding of Nickel(II) and Copper(II) to the N-Terminal Sequence of Human Protamine HP2

A potentiometric and spectroscopic (UV/vis and CD) study of Cu(II) and Ni(II) binding to the N-terminal pentadecapeptide of human protamine HP2 (HP2<INF>1</INF><INF>-</INF><INF>15</INF>) was performed. The results indicate that the N-terminal tripeptide motif Arg-Thr-His is the exclusive binding site for both metal ions at a metal to HP2<INF>1</INF><INF>-</INF><INF>15</INF> molar ratio not higher than 1. The very high value of protonation-corrected stability constant (log *K) for Ni(II)-HP2<INF>1</INF><INF>-</INF><INF>15</INF> complex, −19.29, indicates that HP2 has the potential to sequester Ni(II) from other peptide and protein carriers, including albumin. The same is likely for Cu(II) (log *K = −13.13). The CD spectra of Cu(II) and Ni(II) complexes of HP2<INF>1</INF><INF>-</INF><INF>15</INF> indicate that the N-terminal metal binding affects the overall conformation of the peptide that, in turn, may alter interaction of HP2 with DNA. These results imply HP2 as a likely target for the toxic metals Ni(II) and Cu(II).