Copper(II) complexation by human and mouse fragments (11–16) of β-amyloid peptide

Abstract

A potentiometric and spectroscopic (UV-Vis, CD, NMR and EPR) study of copper() bonding to the N-terminal (11-16) of human and mouse fragments of β-amyloid peptide (EVHHQK-NH 2 , EVRHQK-NH 2 and their Nblocked derivatives) was performed. The results indicate that the hexapeptide amide EVHHQK-NH 2 forms in the pH range 4.5-10.5 complexes in which the coordination of copper() is typical {NH 2 , 2N Ϫ , N Im } for the peptide sequence Xaa-Yaa-His. The mouse fragment containing the N-terminal amino group free in a wide pH range is coordinated through the terminal amino group, carbonyl oxygen or one or two deprotonated amide nitrogens from the N-termini, while the fourth coordination site is occupied by a nitrogen donor of imidazole in the form of a macrochelate. When the amino group is blocked (Ac-EVRHQK-NH 2 ) the imidazole nitrogen of the histidine residue acts as an anchoring bonding site and at higher pH the 3N and 4N complexes are formed with the amide nitrogens coordinated. A blocked hexapeptide modeling a part of human β-amyloid peptide (Ac-EVHHQK-NH 2 ) forms complexes with coordination through imidazole nitrogens both of histidine residues over a broad pH range. With increasing pH the amide nitrogens are also coordinated. In a wide pH range including physiological, Ac-EVHHQK-NH 2 (human fragment) is much more effective in copper() ion bonding than is Ac-EVRHQK-NH 2 (mouse fragment).

The role of terminal amino group and histidine at the fourth position in the metal ion binding of oligopeptides revisited: Copper(II) and nickel(II) complexes of glycyl-glycyl-glycyl-histamine and its N-Boc protected derivative

“…The determined spectroscopic parameters of Cu(BGGGHa) ( Table 2), represent a stronger ligand field around copper(II). In line with previous findings, a macrochelate formation with participation of the N-terminal amino group and the imidazole moiety can be suggested [1,9,13,16,18].…”

“…Amongst basic conditions penta-and hexapeptides of the above type and several other shorter sequences form {NH 2 ,3 × N amide } coordinated complexes, i.e. the imidazole moiety is released from the coordination sphere of copper(II) [16][17][18][19][20]. There are, however, some other examples with larger peptides, where {3 × N amide ,N im } donor set was suggested [21][22][23].…”

Possible involvement of copper(II) in Alzheimer disease.

“…The presence of histidine residue in the 13th position of human fragment changes the coordination mode of Cu(II) ions compared with the mouse fragment. The human fragment of Aβ peptide is much more effective in Cu(II) ion binding than the mouse fragment because of the presence of the His-His sequence (30). These differences in the coordination modes of Cu(II) ions may influence Cu(II) ion-catalyzed oxidation of these peptides by hydrogen peroxide (31).…”

“…The studies on the binding abilities of the various fragments of human and mouse Aβ peptide with Cu 2+ (fragments 1-6, 1-9, 1-10, 11-16) (29,30) have shown that tyrosine residue in the 10th position of the human fragment does not take part in the coordination of the metal ion. The presence of the bulky arginine residue in the 5th position of the peptide sequence of the human fragments changes the coordination ability of the peptide.…”

Stimuli-responsive poly(ampholyte)s containing L-histidine residues: synthesis and protonation thermodynamics of methacrylic polymers in the free and in the cross-linked gel forms

“…Besides the buffering capacity of proteins in the physiological pH range, the imidazole group is also able to form coordination compounds with metal ions [8]. These compounds are considered as models for the understanding of the biological activity of proteins involved in fatal disorders such as the Alzheimer's disease or the prion infection [9,10]. Synthetic polymers containing the imidazole functionality have recently been reported as thermosensitive, reusable displacers for immobilized metal affinity chromatography of proteins [11,12].…”