Competition between the albumin and three histidine fragment of amyloid precursor protein sites to bind Cu(II)

The aim of this work was to check experimentally the relationship between the five-nitrogen donor system {3 × Nimid, 2 × N−} seen e.g. in the peptide fragments of the cysteine-rich amyloid precursor protein (APP) region and the albumin-like {NH2, 2 × N−, Nimid} coordination site. The protected and unprotected octadecapeptides DAHQERMDVSETHLHWHT and Ac-DAHQERMDVSETHLHWHT-NH2 were synthesized and potentiometric and spectroscopic studies were performed. A comparison of both metal-binding sites that occur in both peptides clearly shows that in the unprotected ligand albumin-like binding is much more efficient than the three His site, although around pH 5 both sites have a comparable ability to bind the Cu(II) ion. However, a comparison of the protected and unprotected peptides with their metal binding sites clearly shows that the three His site is very efficient in binding Cu(II) although less effective than the albumin-like motif.

The present paper reports the results of combined potentiometric and spectroscopic studies on the copper(II) complexes of two octadecapeptides (DAHQERMDVSETHLHWHT and Ac-DAHQERMDVSETHLHWHT-NH2) having two distinct metal-binding-domains, the albumin-like N-terminal (DAH) and APP cysteine-rich three His. The -HXHYH- motif is very effective in binding metal ion although it is unable to compete with albumin-like coordination mode in unprotected peptide.Figure optionsDownload as PowerPoint slide