Karavelas T, Malandrinos G, Hadjiliadis N, Mlynarz Piotr, Kozlowski Henryk, Barsan M, Butler I
University of Ioannina, Department of Chemistry, Ioannina, 45110, Greece.
Dalton Trans. 2008 Mar 7(9):1215-23. doi: 10.1039/b716863b. Epub 2007 Dec 21.
In order to reveal more information about the toxicity caused by metals and furthermore their influence to the physiological metabolism of the cell, the hexapeptide model Ac-ThrTyrThrGluHisAla-am representing the C-terminal 71-76 fragment of histone H4 which lies into the nucleosome core, was synthesized. A combined pH-metric and spectroscopic UV-VIS, EPR, CD and NMR study of Ni(II) and Cu(II) binding to the blocked hexapeptide, revealed the formation of octahedral complexes involving imidazole nitrogen of histidine, at pH 5 and pH 7 for Cu(II) and Ni(II) ions respectively. In basic solutions a major square-planar 4 N Ni(II)-complex, adopting a {N(Im), 3N(-)} coordination mode, was formed. In the case of Cu(II) ions, a 3 N complex, involving the imidazole nitrogen of histidine and two deprotonated amide nitrogens of the backbone of the peptide, at pH 7 and a series of 4 N complexes starting at pH 6.5, were suggested. In addition Ni(II)-mediated hydrolysis of the peptide bond-Tyr-Thr was evident following our experimental data.
为了揭示更多关于金属毒性的信息以及它们对细胞生理代谢的影响，合成了代表位于核小体核心的组蛋白H4 C端71 - 76片段的六肽模型Ac - ThrTyrThrGluHisAla - am。通过pH滴定法以及紫外可见光谱、电子顺磁共振、圆二色光谱和核磁共振等光谱学方法对Ni(II)和Cu(II)与封闭六肽的结合进行研究，结果表明，在pH为5时，Cu(II)形成八面体配合物，涉及组氨酸的咪唑氮；在pH为7时，Ni(II)形成八面体配合物，也涉及组氨酸的咪唑氮。在碱性溶液中，形成了主要的平面四方4N Ni(II)配合物，其采用{N(Im), 3N(-)}配位模式。对于Cu(II)离子，在pH为7时形成了一种3N配合物，涉及组氨酸的咪唑氮和肽主链上的两个去质子化酰胺氮，在pH为6.5时开始形成一系列4N配合物。此外，根据我们的实验数据，Ni(II)介导的肽键 - Tyr - Thr水解是明显的。
