Cu(II) complexes with peptides from FomA protein containing -His-Xaa-Yaa-Zaa-His and -His-His-motifs. ROS generation and DNA degradation
Cu(II) complexes with peptides from FomA protein containing -His-Xaa-Yaa-Zaa-His and -His-His-motifs. ROS generation and DNA degradation
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DOI：
10.1016/j.jinorgbio.2020.111250
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发表时间：
2020-11-01
影响因子：
3.9
通讯作者：
Ptaszynska, Natalia
中科院分区：
文献类型：
--
作者：
Lesiow, Monika Katarzyna;Bienko, Alina;Ptaszynska, Natalia
采用电位测定法、光谱法（UV-Vis、CD、EPR）和 MS 技术研究了具有具核梭杆菌 FomA 蛋白的 Ac-PTVHNEYH-NH2 (L1) 和 Ac-NHHTLND-NH2 (L2) 肽的单核和双核 Cu(II) 配合物。 L1 配体的主要单核配合物是：具有 2N {2N(im)} 的 CuHL（pH 范围 5.0-6.0）、CuH-2L（pH 范围 8.0-8.5）和具有 4N {N-im, 3N(-)} 配位模式的 CuH-3L 物质（pH 9.0 以上）。配合物：具有 3N {2N(im), N-} 的 CuH-1L、具有 3N {N-im, 2N(-)} 的 CuH-2L 和具有 4N {N-im, 3N(-)} 结合位点的 CuH-3L 被提议用于 L2 配体。可能在 CuL2 系统的 CuH-2L 复合物中，His-His 序列中的第二个 His 残基与 Cu(II) 离子结合，而第一个 His 残基可以通过 His-His 和/或 His-Cu(II) 相互作用稳定该复合物。 pH 范围 6.5-10.5 内的主要双核 Cu(2)L1 配合物是：Cu2H-4L 和 Cu2H-6L 物质，分别具有 3N{N-im, 2N-}4N{N-im, 3N(-)} 和 4N{N-im, 3N(-)}4N{N-im, 3N(-)} 结合位点。对于 pH 值范围为 7.2-10.5 的 Cu(2)L2 配合物，Cu2H-4L 和 Cu2H-7L 物质分别以 2N{N-im, N-}4N{N-im, 3N(-)} 和 (Cu(OH)(4)(2-)4N{N-im, 3N(-)}) 配位模式占主导地位。研究了在过氧化氢或抗坏血酸存在下，pH 7.4 下未络合的 Cu(II) 离子、配体及其络合物产生活性氧 (ROS) 的能力。使用UV-Vis、发光、EPR 自旋捕获和凝胶电泳方法。与它们的配体相比，这两种复合物产生更高水平的ROS。 Cu(II) 复合物产生的 ROS 是羟基自由基和单线态氧，有助于氧化 DNA 裂解。
Monoand dinuclear Cu(II) complexes with Ac-PTVHNEYH-NH2 (L1) and Ac-NHHTLND-NH2 (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(im)}, CuH-2L (pH range 8.0-8.5) and CuH-3L species (above pH 9.0) with 4N {N-im, 3N(-)} coordination modes. The complexes: CuH-1L with 3N {2N(im), N-}, CuH-2L with 3N {N-im, 2N(-)} and CuH-3L with 4N {N-im, 3N(-)} binding sites are proposed for the L2 ligand. Probably in the CuH-2L 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 Cu(2)L1 complexes in the pH range 6.5-10.5 are: the Cu2H-4L and Cu2H-6L species with 3N{N-im, 2N-}4N{N-im, 3N(-)} and 4N{N-im, 3N(-)}4N{N-im, 3N(-)} binding sites, respectively. In the case of the Cu(2)L2 complex in the pH range 7.2-10.5, the Cu2H-4L and Cu2H-7L species dominate with 2N{N-im, N-}4N{N-im, 3N(-)} and (Cu(OH)(4)(2-)4N{N-im, 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.