title: High stability and biological activity of the copper(II) complexes of alloferon 1 analogues containing tryptophan.
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 pH7.4 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 4N 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 pH7.4 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 pH7.4.
authors.affiliation: Faculty of Chemistry, University of Wrocław, Joliot-Curie 14, 50-383 Wrocław, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Kadej
authors.affiliation: Faculty of Chemistry, University of Wrocław, Joliot-Curie 14, 50-383 Wrocław, Poland.
authors.forename: Mariola
authors.initials: M
authors.lastname: Kuczer
authors.affiliation: Department of Animal Physiology and Development, Institute of Experimental Biology, Adam Mickiewicz University, Umultowska 89, 61-614 Poznań, Poland.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Czarniewska
authors.affiliation: Department of Animal Physiology and Development, Institute of Experimental Biology, Adam Mickiewicz University, Umultowska 89, 61-614 Poznań, Poland; Department of Systematic Zoology, Adam Mickiewicz University, Umultowska 89, 61-614 Poznań, Poland.
authors.forename: Arkadiusz
authors.initials: A
authors.lastname: Urbański
authors.affiliation: Department of Animal Physiology and Development, Institute of Experimental Biology, Adam Mickiewicz University, Umultowska 89, 61-614 Poznań, Poland.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Rosiński
authors.affiliation: Faculty of Chemistry, University of Wrocław, Joliot-Curie 14, 50-383 Wrocław, Poland. Electronic address: teresa.kowalik-jankowska@chem.uni.wroc.pl.
authors.forename: Teresa
authors.initials: T
authors.lastname: Kowalik-Jankowska
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D003300:Copper / Q000737:chemistry / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D013712:Tenebrio / Q000378:metabolism*; D014364:Tryptophan / Q000737:chemistry / Q000494:pharmacology
chemical_list: C510535:Alloferon; D010455:Peptides; D003300:Copper; D014364:Tryptophan
keywords: Biological activity; Copper(II) complexes; Stability constants; Tryptophan analogues of alloferon 1