| Autor: |
Wezynfeld NE; Chair of Medical Biotechnology, Faculty of Chemistry, Warsaw University of Technology, Noakowskiego 3, 00-664 Warsaw, Poland., Tobolska A; Chair of Medical Biotechnology, Faculty of Chemistry, Warsaw University of Technology, Noakowskiego 3, 00-664 Warsaw, Poland.; Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland., Mital M; Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a, 02-106 Warsaw, Poland., Wawrzyniak UE; Chair of Medical Biotechnology, Faculty of Chemistry, Warsaw University of Technology, Noakowskiego 3, 00-664 Warsaw, Poland., Wiloch MZ; Charge Transfer Processes in Hydrodynamic Systems Group, Institute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland., Płonka D; Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a, 02-106 Warsaw, Poland., Bossak-Ahmad K; Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a, 02-106 Warsaw, Poland., Wróblewski W; Chair of Medical Biotechnology, Faculty of Chemistry, Warsaw University of Technology, Noakowskiego 3, 00-664 Warsaw, Poland., Bal W; Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a, 02-106 Warsaw, Poland. |
| Abstrakt: |
The Aβ 5- x peptides ( x = 38, 40, 42) are minor Aβ species in normal brains but elevated upon the application of inhibitors of Aβ processing enzymes. They are interesting from the point of view of coordination chemistry for the presence of an Arg-His metal binding sequence at their N-terminus capable of forming a 3-nitrogen (3N) three-coordinate chelate system. Similar sequences in other bioactive peptides were shown to bind Cu(II) ions in biological systems. Therefore, we investigated Cu(II) complex formation and reactivity of a series of truncated Aβ 5- x peptide models comprising the metal binding site: Aβ 5-9 , Aβ 5-12 , Aβ 5-12 Y10F, and Aβ 5-16 . Using CD and UV-vis spectroscopies and potentiometry, we found that all peptides coordinated the Cu(II) ion with substantial affinities higher than 3 × 10 12 M -1 at pH 7.4 for Aβ 5-9 and Aβ 5-12 . This affinity was elevated 3-fold in Aβ 5-16 by the formation of the internal macrochelate with the fourth coordination site occupied by the imidazole nitrogen of the His13 or His14 residue. A much higher boost of affinity could be achieved in Aβ 5-9 and Aβ 5-12 by adding appropriate amounts of the external imidazole ligand. The 3N Cu-Aβ 5- x complexes could be irreversibly reduced to Cu(I) at about -0.6 V vs Ag/AgCl and oxidized to Cu(III) at about 1.2 V vs Ag/AgCl. The internal or external imidazole coordination to the 3N core resulted in a slight destabilization of the Cu(I) state and stabilization of the Cu(III) state. Taken together these results indicate that Aβ 5- x peptides, which bind Cu(II) ions much more strongly than Aβ 1- x peptides and only slightly weaker than Aβ 4- x peptides could interfere with Cu(II) handling by these peptides, adding to copper dyshomeostasis in Alzheimer brains. |
