Copper(II) Coordination Abilities of the Tau Protein's N-Terminus Peptide Fragments: A Combined Potentiometric, Spectroscopic and Mass Spectrometric Study

Abstract

Copper(II) complexes of the N-terminal peptide fragments of tau protein have been studied by potentiometric and various spectroscopic techniques (UV-vis, CD, ESR and ESI-MS). The octapeptide Tau(9-16) (Ac−EVMEDHAG−NH2) contains the H14 residue of the native protein, while Tau(26-33) (Ac−QGGYTMHQ−NH2) and its mutants Tau(Q26K-Q33K) (Ac−KGGYTMHK−NH2) and Tau(Q26K-Y29A-Q33K) (Ac−KGGATMHK−NH2) include the H32 residue. To compare the binding ability of H14 and H32 in a single molecule the decapeptide Ac−EDHAGTMHQD−NH2 (Tau(12-16)(30-34)) has also been synthesized and studied. The histidyl residue is the primary metal binding site for metal ions in all the peptide models studied. In the case of Tau(9-16) the side chain carboxylate functions enhance the stability of the M−Nim coordinated complexes compared to Tau(26-33) (logK(Cu−Nim)=5.04 and 3.78, respectively). Deprotonation and metal ion coordination of amide groups occur around the physiological pH range for copper(II). The formation of the imidazole- and amide-coordinated species changes the metal ion preference and the complexes formed with the peptides containing the H32 residue predominate over those of H14 at physiological pH values (90 %–10 %) and in alkaline samples (96 %–4 %).