Cu(II) complexes with peptides from FomA protein containing -His-Xaa-Yaa-Zaa-His and -His-His-motifs. ROS generation and DNA degradation.

Mono- and dinuclear Cu(II) complexes with Ac-PTVHNEYH-NH (L1) and Ac-NHHTLND-NH (L2) peptides from FomA protein of Fusobacterium nucleatum were studied by potentiometry, spectroscopic methods (UV-Vis, CD, EPR) and MS technique. The dominant mononuclear complexes for L1 ligand are: CuHL (pH range 5.0-6.0) with 2N {2N}, CuHL (pH range 8.0-8.5) and CuHL species (above pH 9.0) with 4N {N, 3N} coordination modes. The complexes: CuHL with 3N {2N, N}, CuHL with 3N {N, 2N} and CuHL with 4N {N, 3N} binding sites are proposed for the L2 ligand. Probably in the CuHL complex for CuL2 system the second His residue in His-His sequence is bound to Cu(II) ion, while the first His residue may stabilize this complex by His-His and/or His-Cu(II) interactions. The dominant dinuclear CuL1 complexes in the pH range 6.5-10.5 are: the CuHL and CuHL species with 3N{N, 2N}4N{N, 3N} and 4N{N, 3N}4N{N, 3N} binding sites, respectively. In the case of the CuL2 complex in the pH range 7.2-10.5, the CuHL and CuHL species dominate with 2N{N, N}4N{N, 3N} and (Cu(OH)4N{N, 3N}) coordination modes, respectively. The ability to generate reactive oxygen species (ROS) by uncomplexed Cu(II) ions, ligands and their complexes at pH 7.4 in the presence of hydrogen peroxide or ascorbic acid was studied. UV-Vis, luminescence, EPR spin trapping and gel electrophoresis methods were used. Both complexes produce higher level of ROS compared to those of their ligands. ROS produced by Cu(II) complexes are hydroxyl radical and singlet oxygen, which contribute to oxidative DNA cleavage.