Di Natale Giuseppe, Grasso Giulia, Impellizzeri Giuseppe, La Mendola Diego, Micera Giovanni, Mihala Nikolett, Nagy Zoltán, Osz Katalin, Pappalardo Giuseppe, Rigó Viktória, Rizzarelli Enrico, Sanna Daniele, Sóvágó Imre
Dipartimento di Scienze Chimiche, Università di Catania, Italy.
Inorg Chem. 2005 Oct 3;44(20):7214-25. doi: 10.1021/ic050754k.
Copper(II) complexes of the neurotoxic peptide fragments of human and chicken prion proteins were studied by potentiometric, UV-vis, CD, and EPR spectroscopic and ESI-MS methods. The peptides included the terminally blocked native and scrambled sequences of HuPrP106-126 (HuPrPAc106-126NH2 and ScrHuPrPAc106-126NH2) and also the nona- and tetrapeptide fragments of both the human and chicken prion proteins (HuPrPAc106-114NH2, ChPrPAc119-127NH2, HuPrPAc109-112NH2, and ChPrPAc122-125NH2). The histidyl imidazole-N donor atoms were found to be the major copper(II) binding sites of all peptides; 3N and 4N complexes containing additional 2 and 3 deprotonated amide-N donors, respectively, are the major species in the physiological pH range. The complex formation processes for nona- and tetrapeptides are very similar, supporting the fact that successive deprotonation and metal ion coordination of amide functions go toward the N-termini in the form of joined six- and five-membered chelates. As a consequence, the peptide sequences investigated here, related to the neurotoxic region of the human PrP106-126 sequence, show a higher metal-binding affinity than the octarepeat fragments. In the case of the HuPrP peptide sequences, a weak pH-dependent binding of the Met109 residue was also detected in the 3N-coordinated complexes.
采用电位滴定法、紫外可见光谱法、圆二色光谱法、电子顺磁共振光谱法和电喷雾电离质谱法，研究了人和鸡朊蛋白神经毒性肽片段的铜（II）配合物。这些肽包括人朊蛋白106 - 126（HuPrPAc106 - 126NH2和ScrHuPrPAc106 - 126NH2）末端封闭的天然和无序序列，以及人和鸡朊蛋白的九肽和四肽片段（HuPrPAc106 - 114NH2、ChPrPAc119 - 127NH2、HuPrPAc109 - 112NH2和ChPrPAc122 - 125NH2）。发现组氨酸咪唑 - N供体原子是所有肽的主要铜（II）结合位点；分别含有另外2个和3个去质子化酰胺 - N供体的3N和4N配合物是生理pH范围内的主要物种。九肽和四肽的配合物形成过程非常相似，这支持了酰胺官能团的连续去质子化和金属离子配位以连接的六元环和五元环螯合物的形式朝向N端进行的事实。因此，这里研究的与人类PrP106 - 126序列的神经毒性区域相关的肽序列显示出比八肽重复片段更高的金属结合亲和力。在HuPrP肽序列的情况下，在3N配位的配合物中还检测到Met109残基的弱pH依赖性结合。
