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Vancomycin, a “last chance” antibiotic, is a glycopeptide consisting of an oligopeptide unit being potentially the effective binder of Cu2ions. The potentiometric and spectroscopic studies UV-Vis, CD, EPR, NMR have shown that, indeed, the peptide unit binds cupric ions very effectively forming almost instantly the 3N complex involving the N-terminal nitrogen donors in the metal ion coordination. The comparison of the binding ability of vancomycin with other peptide chelators clearly shows the efficiency of this antibiotic in metal ion coordination. It is very likely that Cu2ions may play a crucial role in the pharmacology of vancomycin, particularly when administered in high doses.

Potentiometric and spectroscopic data have shown that octarepeat dimer and tetramer are much more effective ligands for Cuii ions than simple octapeptide. Thus, the whole N-terminal segment of prion protein due to cooperative effects, could be more effective in binding of Cuii than simple peptides containing a His residue. The gain of the Cuii binding by longer octarepeat peptides derives from the involvement of up to four imidazoles in the coordination of the first Cuii ion. This type of binding increases the order of the peptide structure, which allows successive metal ions for easier coordination.

The copper(ii) binding features of the APP(145–155) and APP(145–157) fragments of the amyloid precursor protein, Ac-Glu-Thr-His-Leu-His-Trp-His-Thr-Val-Ala-Lys-NH₂ and Ac-Glu-Thr-His-Leu-His-Trp-His-Thr-Val-Ala-Lys-Glu-Thr-NH₂ were studied by NMR spectroscopy and NMR findings were supported by UV-vis, CD and EPR spectra. Potentiometric measurements were performed only for the more soluble Ac-Glu-Thr-His-Leu-His-Trp-His-Thr-Val-Ala-Lys-Glu-Thr-NH₂ peptide fragment. The following was shown: (i) the imidazole rings of all the three His residues are involved in metal coordination; (ii) metal binding induces ionisation of Leu-148 and His-149 amide nitrogens that complete the donor set to copper(ii) in the species dominant at neutral pH; (iii) the unusual coordination scheme of the His-Xxx-His-Xxx-His consensus sequence justifies the high specificity for Cu(ii) when compared to SOD-like or albumin-like peptides or even in amyloid Aβ fragments. The present findings may represent the key for interpreting the observed requirement of His residues conservation for the redox cycling between Cu(ii) and Cu(i) by soluble APP.

The copperii binding features of the APP145–155 and APP145–157 fragments of the amyloid precursor protein, Ac-Glu-Thr-His-Leu-His-Trp-His-Thr-Val-Ala-Lys-NH2and Ac-Glu-Thr-His-Leu-His-Trp-His-Thr-Val-Ala-Lys-Glu-Thr-NH2were studied by NMR spectroscopy and NMR findings were supported by UV-vis, CD and EPR spectra. Potentiometric measurements were performed only for the more soluble Ac-Glu-Thr-His-Leu-His-Trp-His-Thr-Val-Ala-Lys-Glu-Thr-NH2peptide fragment. The following was shown: (i the imidazole rings of all the three His residues are involved in metal coordination; (ii metal binding induces ionisation of Leu-148 and His-149 amide nitrogens that complete the donor set to copperii in the species dominant at neutral pH; (iii the unusual coordination scheme of the His-Xxx-His-Xxx-His consensus sequence justifies the high specificity for Cuii when compared to SOD-like or albumin-like peptides or even in amyloid Aβ fragments. The present findings may represent the key for interpreting the observed requirement of His residues conservation for the redox cycling between Cuii and Cui by soluble APP.