Metal complexation by the peptide-bound maillard reaction products N(epsilon)-fructoselysine and N(epsilon)-carboxymethyllysine

J Agric Food Chem. 2004 Apr 21;52(8):2347-50. doi: 10.1021/jf035223y.


Although the Maillard reaction between proteins and carbohydrates is of central importance for food processing and in vivo processes, only little is known about changes of the metal-binding properties induced by protein glycation. The purpose of this study was to examine the complex formation of the quantitatively important peptide-bound Maillard reaction products (MRPs) N(epsilon)-fructoselysine and N(epsilon)-carboxymethyllysine with the biologically relevant metal ions copper(II) and zinc(II). The MRPs were synthesized as the N(alpha)-hippuryllysine derivatives in order to block the coordination function of the alpha-amino group. Stability constant measurements were performed in aqueous solution using pH potentiometry. N(alpha)-Hippuryl-N(epsilon)-fructoselysine forms moderate Cu(II) complexes (Log(10) K(1) = 5.8; Log(10) K(2) = 4.0) but fails to form any complexes with Zn(II). N(alpha)-Hippuryl-N(epsilon)-carboxymethyllysine gives slightly stronger complexes with Cu(II) (Log(10) K(1) = 7.3; Log(10) K(2) = 6.3), but again no complexation with Zn(II) was observed. These results show that post-translational modification of proteins by carbohydrates leads to the formation of new coordination centers for metal ions within a protein chain. Further studies are necessary to clarify the consequences of this phenomenon in terms of protein quality and physiological processes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Copper / chemistry
  • Lysine / analogs & derivatives*
  • Lysine / chemistry*
  • Maillard Reaction*
  • Metals / chemistry*
  • Peptides / chemistry*
  • Zinc / chemistry


  • Metals
  • Peptides
  • fructosyl-lysine
  • N(6)-carboxymethyllysine
  • Copper
  • Zinc
  • Lysine