Metal Binding Ability of Small Peptides Containing Cysteine Residues

Abstract

The Cd(II)-, Pb(II)-, Ni(II)- and Zn(II)-complexes of small terminally protected peptides containing CXXX, XXXC, XCCX, CX_n C (n=1-3) sequences have been studied with potentiometric, UV/Vis and CD spectroscopic techniques. The cysteine thiolate group is the primary binding site for all studied metal ions, but the presence of a histidyl or aspartyl side chain in the molecule contributes to the stability of the complexes. For two-cysteine containing peptides the (S^- ,S^- ) coordinated species are formed in the physiological pH range and the stability increases in the Ni(II)<Zn(II)<Pb(II)<Cd(II) order. As a conclusion, the inserting of -CXXC- sequence into the peptide makes the synthesis of peptides with high selectivity to toxic Cd(II) or Pb(II) ion possible. In addition, the spectroscopic characterization of these complexes can contribute to the discovery of the exact binding site and binding mode of longer peptides mimicking the biologically important proteins.

Keywords: cysteine containing peptides; metal complexes; selectivity; spectroscopic measurements; stability constant.

Figure 1

Stability constants (logβ) of Zn(II) and Cd(II) complexes with different binding modes (data from ref. [33], [34] and [42]).

Figure 2

Concentration distribution curves of the species formed in Ni(II)‐AAAC 1 : 2 (a), Ni(II)‐CGAA 1 : 2 (b) systems (c_L=1 mM).

Figure 3

Change of the molar absorptivity of Ni(II):Ac‐CGAH‐NH₂ 1 : 1 and 1 : 2 solutions at 408 nm in the function of equivalent of base (c_L=1 mM).

Figure 4

The CD spectra of [NiH₋₃L] complexes of different tetrapeptides containing cysteinyl residue in the C‐termini (a) and N‐termini (b).

Scheme 1

The schematic structures of [NiH₋₃L] complexes of tetrapeptides: Ac‐AAAC‐NH₂ (a), Ac‐CGAX‐NH₂, X=A, D or K (b) and Ac‐CGAH‐NH₂ (c).

Scheme 2

The schematic structures of [Ni₃L₄] (a), [(Ni₂H₋₂L₂])_x] (b), [NiH₋₂L] (c) and [NiH₋₃L] (d) complexes.

Figure 5

Concentration distribution curves of equimolar solution of Ni(II):Ac‐SCCS‐NH₂ (a), Ni(II):Ac‐CSC‐NH₂ (b), Ni(II):Ac‐CSSC‐NH₂ (c) and Ni(II):Ac‐CSSACS‐NH₂ (d) systems and the absorption values at 419–433 nm in function of pH (c_L=1 mM).

Figure 6

CD spectra of [NiH₋₂L]/ [(Ni₂H₋₃L₂)_x] (a) and [NiH₋₃L] (b) complexes of peptides containing two cysteinyl residues.

Figure 7

Concentration distribution curves of model system containing Cd(II) : Pb(II) : Zn(II) : Ni(II) : Ac‐CSSC‐NH₂ in 1 : 1 : 1 : 1 : 1 ratio (c_L=1 mM).

Scheme 3

Structural formulae of the studied peptides.