Title
High stability and biological activity of the copper(II) complexes of alloferon 1 analogues containing tryptophan
Author
Agnieszka Kadej, Mariola Kuczer, Elżbieta Czarniewska, Arkadiusz Urbański, Grzegorz Rosiński, Teresa Kowalik-Jankowska
Year
2016
Journal
Journal of Inorganic Biochemistry
Abstract
Copper(II) complex formation processes between the alloferon 1 (Allo1) (HGVSGHGQHGVHG) analogues where the tryptophan residue is introducing in the place His residue H1W, H6W, H9W and H12W have been studied by potentiometric, UV–visible, CD and EPR spectroscopic, and MS methods. For all analogues of alloferon 1 complex speciation have been obtained for a 1:1 metal-to-ligand molar ratio and 2:1 of H1W because of precipitation at higher (2:1, 3:1 and 4:1) ratios. At physiological pH 7.4 and a 1:1 metal-to-ligand molar ratio the tryptophan analogues of alloferon 1 form the CuH− 1L and/or CuH− 2L complexes with the 4 N binding mode. The introduction of tryptophan in place of histidine residues changes the distribution diagram of the complexes formed with the change of pH and their stability constants compared to the respective substituted alanine analogues of alloferon 1. The CuH− 1L, CuH− 2L and CuH− 3L complexes of the tryptophan analogues are more stable from 1 to 5 log units in comparison to those of the alanine analogues. This stabilization of the complexes may result from cation(Cu(II))-π and indole/imidazole ring interactions. The induction of apoptosis in vivo, in Tenebrio molitor cells by the ligands and their copper(II) complexes at pH 7.4 was studied. The biological results show that copper(II) ions in vivo did not cause any apparent apoptotic features. The most active were the H12W peptide and Cu(II)-H12W complex formed at pH 7.4.
Instrument
J-715
Keywords
Circular dichroism, Ligand binding, Inorganic chemistry, Biochemistry