Cu^II Ion Coordination to an Unprotected Pentadecapeptide Containing Two His Residues: Competition Between the Terminal Amino and the Side‐Chain Imidazole Nitrogen Donors

Abstract

The complex-formation equilibria of the pentadecapeptide TLEGTKKGHKLHLDY, the 114-128 protein fragment of SPARC, with the Cull ion have been investigated, at I = 0.1 mol.dm(-3) (KNO3) and T = 298.2 K. Protonation and complex-formation constants have been determined potentiometrically, and formation enthalpies measured by direct solution calorimetry; the complex-formation model and species stoichiometry have been carefully checked by means of UV/Vis absorption, CD and EPR spectroscopy. The structure hypo-theses of the complex species are also based on detailed study of the H-1 and C-13 NMR spectra of the ligand in both the absence and presence of copper ions. The involvement in complex-formation of both the terminal amino and imidazole groups has been suggested and their specific behaviour at different pH values elucidated

Copper Binding to the Neurotoxic Peptide PrP106–126: Thermodynamic and Structural Studies

“…Thermodynamic results on protonation equilibria are reported in Tables 1 and 2; they are in good agreement with previous results on similar systems 20…”

“…In the latter species the donor centres are just an amino and an imidazole group, as hypothesized for this MLH 2 species. A macrochelate ring should form in this case, as already previously reported in literature for an unprotected pentadecapeptide derived from the SPARC protein 20…”

“…The most basic sites are the side chain amino groups of Lys106 and Lys110 (see Tables 1 and 2): according to previous data on peptides also containing one or more lysine residues,20, 26 they should be protonated. From the present data, it cannot be said whether the copper‐promoted deprotonation takes place at the terminal amino group, as usually happens with unprotected peptides,30 or at the imidazole nitrogen of His111 residue, as already reported with protected His‐containing peptides 20. Competition between the two donor sites is most probably operative, as found previously 26.…”

“…A further ”blue shift” is recorded in VIS spectra (see Supporting Information and Tables 4 and 6); this suggests the coordination of another nitrogen atom to the metal. Taking into account that the side amino group of Lys residues do not normally bind copper in this pH range,20, 26, 32 the deprotonation of an amido nitrogen of a peptide bond and its coordination to the metal ion are suggested. This normally happens, from pH 5 onwards, with short peptides 30.…”

The rotating ring-disk electrochemistry of the copper(II) complex of thyrotropin-releasing hormone

“…The interactions of a-synuclein, the protein responsible for the Lewy bodies of Parkinson's disease, with Cu(II) are considered important [17]. The details of the coordination chemistry of copper complexes of peptides are keys to understanding the many roles -both normal and pathological -of copper-peptide systems [16,18,19].…”