Copper(II) Interaction with Unstructured Prion Domain Outside the Octarepeat Region: Speciation, Stability, and Binding Details of Copper(II) Complexes with PrP106-126 Peptides

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• 作者：Giuseppe Di Natale ; Giulia Grasso ; Giuseppe Impellizzeri ; Diego La Mendola ; Giovanni Micera ; Nikolett Mihala ; Zoltá ; n Nagy ; Katalin Õ ; sz ; Giuseppe Pappalardo ; Vikt&oacute ; ria Rig&oacute
• 刊名：Inorganic Chemistry
• 出版年：2005
• 出版时间：October 3, 2005
• 年：2005
• 卷：44
• 期：20
• 页码：7214 - 7225
• 全文大小：191K
• 年卷期：v.44,no.20(October 3, 2005)
• ISSN：1520-510X

文摘

Copper(II) complexes of the neurotoxic peptide fragments of human and chicken prion proteins were studied bypotentiometric, UV-vis, CD, and EPR spectroscopic and ESI-MS methods. The peptides included the terminallyblocked 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 donoratoms were found to be the major copper(II) binding sites of all peptides; 3N and 4N complexes containing additional2 and 3 deprotonated amide-N donors, respectively, are the major species in the physiological pH range. Thecomplex formation processes for nona- and tetrapeptides are very similar, supporting the fact that successivedeprotonation and metal ion coordination of amide functions go toward the N-termini in the form of joined six- andfive-membered chelates. As a consequence, the peptide sequences investigated here, related to the neurotoxicregion 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 alsodetected in the 3N-coordinated complexes.