NR AVDB
AU Di Natale,G.; Grasso,G.; Impellizzeri,G.; La Mendola,D.; Micera,G.; Mihala,N.; Nagy,Z.; Osz,K.; Pappalardo,G.; Rigo,V.; Rizzarelli,E.; Sanna,D.; Sovago,I.
TI Copper(II) interaction with unstructured prion domain outside the octarepeat region: speciation, stability, and binding details of copper(II) complexes with PrP106-126 peptides.
QU Inorganic Chemistry 2005 Oct 3; 44(20): 7214-25
PT journal article
AB 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.
MH Amino Acid Sequence; Animals; Chickens; Circular Dichroism; Copper/*chemistry; Drug Stability; Electron Spin Resonance Spectroscopy; Humans; Molecular Sequence Data; Peptide Fragments/chemical synthesis/*chemistry; Potentiometry; Prions/*chemistry; Research Support, Non-U.S. Gov't; Spectrometry, Mass, Electrospray Ionization; Spectrophotometry
AD Dipartimento di Scienze Chimiche, Universita di Catania, Italy.
SP englisch
PO USA