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Peptide–Metal Interactions

  1. Claude F. Meares

Published Online: 15 DEC 2011

DOI: 10.1002/9781119951438.eibc0167

Encyclopedia of Inorganic and Bioinorganic Chemistry

Encyclopedia of Inorganic and Bioinorganic Chemistry

How to Cite

Meares, C. F. 2011. Peptide–Metal Interactions . Encyclopedia of Inorganic and Bioinorganic Chemistry. .

Author Information

  1. University of California, Davis, CA, USA

Publication History

  1. Published Online: 15 DEC 2011

Abstract

Copper–peptide complexes have been the most extensively studied of all the metal–peptide complexes. Copper(II) is the most important oxidation state in copper–peptide complexes, although copper(III) can be stabilized by coordination to peptides. The deprotonated peptide nitrogens help stabilize the higher oxidation state of copper; therefore the more deprotonated peptide nitrogens, the more stable the copper(III) complex. The copper(II) complexes of Gly[BOND]Gly[BOND]Pro[BOND]Gly and (Gly[BOND]Gly[BOND]Pro[BOND]Gly)2 are very similar. At low pH, both peptides bond through the amino nitrogen and carbonyl oxygen of the first peptide linkage. The peptides Gly[BOND]Gly[BOND]Pro[BOND]Lys and (Gly[BOND]Gly[BOND]Pro[BOND]Lys)2 initially form 1N complexes with copper(II). With luteinizing hormone-releasing hormone the copper(II) is coordinated via the imidazole nitrogen and two deprotonated peptide nitrogens. With angiotensin II, the copper(II) is bonded via the imidazole nitrogen of the histidine residue and two deprotonated peptide nitrogens. The dipeptide Tyr[BOND]Pro bonded copper(II) through the amino nitrogen and the peptide carbonyl. Since there was no ionizable hydrogen on the peptide nitrogen, there was no bonding by the peptide nitrogen. The copper(II)[BOND]AVP (vasopressin analog) complex is one of the most stable 4N copper–peptide complexes known. Owing to their similarities, nickel(II)–peptide complexes are usually studied along with copper(II) complexes. In neutral to acidic solutions, the nickel is coordinated through the amino nitrogen and the carbonyl oxygen (1N). When the pH is raised to 9.0, nickel(II) substitutes for a peptide hydrogen, and the coordination changes. In NiH[BOND]1L complexes of cysteine-containing dipeptides, the nickel is coordinated via the amino and deprotonated peptide nitrogens and the thiol group. Zinc-peptide complexes are less stable. With the dipeptides Ala–His and Gly–His at high pH, zinc(II) was shown to form complexes coordinated through the amino nitrogen, deprotonated peptide nitrogen, and the imidazole nitrogen. Unlike copper(II), both palladium(II) and platinum(II) are soft acceptors and as such are expected to coordinate to soft donors like sulfur and aromatic nitrogen donors in residues such as Met and His, and deprotonated peptide nitrogens. Early investigations of metals showed that divalent metals such as copper(II), cobalt(II), and nickel(II) could catalyze the hydrolysis of amino acid esters. Mechanisms of cobalt(III)-mediated peptide-bond cleavage have been investigated; because cobalt(III) complexes bind to the N-terminal amino acid residue of peptides, only the N-terminal peptide bond is hydrolyzed. Complexes containing iron can cleave peptide bonds, as can complexes of palladium or platinum.

Keywords:

  • tuftsin;
  • luteinizing hormone-releasing hormone (LHRH);
  • thyrotropin releasing factor (TRF);
  • angiotensin II;
  • bleomycin;
  • fibrinopeptide A;
  • vasopressin;
  • cleavage;
  • hydrolysis