Copper(ii) complexes of terminally protected pentapeptides containing three histidyl residues in alternating positions, Ac-His-Xaa-His-Yaa-His-NH₂

Abstract

Copper(II) complexes of the pentapeptides Ac-HisAlaHisValHis-NH2, Ac-HisValHisAlaHis-NH2, Ac-HisProHisAlaHis-NH2, Ac-HisAlaHisProHis-NH2, Ac-HisGlyHisValHis-NH2 and Ac-HisValHisGlyHis-NH2 have been studied by potentiometric, UV-Vis, CD and EPR spectroscopic methods. It has been found that the pentapeptides are efficient ligands for the complexation with copper(II) and exhibit an outstanding versatility in the co-ordination geometry of complexes. The presence of three histidyl residues provides a high possibility for the formation of macrochelates via the exclusive binding of imidazole-N donor atoms. The macrochelation suppresses, but cannot preclude the deprotonation and metal ion co-ordination of amide functions and the species [CuH(-2)L] and [Cu2H(-4)L] predominate at physiological pH in equimolar solutions and in the presence of excess metal ions, respectively. It is also clear from the data that both C-terminal and internal histidyl residues can work as the anchoring sites for metal binding and subsequent amide deprotonation resulting in the formation of co-ordination isomers and dinuclear species in equimolar solutions and in the presence of excess metal ions, respectively. In more alkaline solutions (pH approximately 10) a third amide function can be deprotonated and co-ordinated in the species [CuH(-3)L]- with (N-,N-,N-,N(im)) co-ordination. The dinuclear species [Cu2H(-5)L]- and [Cu2H(-6)L](2-) containing hydroxide ions and/or imidazolato bridges are formed at high pH in the presence of excess of metal ions. The insertion of one proline into the sequence preceding histidyl residues hinders the deprotonation of amide functions at that site and the formation of only mononuclear complexes was observed with these peptides.

Probing the Cu2+ and Zn2+ binding affinity of histidine-rich glycoprotein

“…The determined pK values (see Table 1) representing the deprotonation processes are macroscopic constants and cannot be assigned to individual histidine residues. The pK values are very similar to those measured for other terminally protected short Hisrich peptides [41,42,[48][49][50][51][52], which reflect no specific interaction between the deprotonating groups of the ligands.…”

Binary and ternary mixed metal complexes of terminally free peptides containing two different histidyl binding sites

“…The studies on the copper(II) complexes of the peptide fragments of prion protein and related substances revealed that the internal histidyl residues can also be anchoring sites for copper(II) or nickel(II) binding [5]. Moreover, the formation of polynuclear copper(II) and/or nickel(II) complexes was observed with various multihistidine peptides [8][9][10][11]. Peptide fragments of prion protein and amyloid-β peptides provided the most evident examples for the binding of more than one copper(II) and nickel(II) ions in these complexes [12][13][14][15][16].…”

Copper(II) Interaction with Prion Peptide Fragments Encompassing Histidine Residues Within and Outside the Octarepeat Domain: Speciation, Stability Constants and Binding Details

“…The value of logKA C H T U N G T R E N N U N G (Cu+3N im ) = 6.47 was obtained for the [CuH 4 L] 6 + species of the 31-mer peptide, while 7.22 and 8.08 were published for the small 3-histidine peptides Ac-HisHisGlyHis-NHMe and Ac-HisAlaHisValHis-NH 2 , respectively; these peptides have similar binding modes. [41,42] According to these data, the stabilities of the macrochelates follow the order HAHVH > HHGH > HuPrPA C H T U N G T R E N N U N G (84-114). The formation of macrochelates with the exclusive metal binding of side-chain imidazole functions have been reported for a series of other peptides that contain two or three histidyl residues and the stability constants were also in the same range.…”

“…The unfavourable consequence is that, because the three binding sites are very similar to each other, the measured EPR spectra resemble those that would be obtained in the case of a system that is formed by a Cu 2 + ion interacting with three ligands that are very similar to each other. In our previous publications [41,42] the parameters A k % 160-170 and 170-180 ( 10 À4 cm…”