title: Copper(II) complexes of alloferon 1 with point mutations (H1A) and (H9A) stability structure and biological activity.
abstract: Mono- and polynuclear copper(II) complexes of the alloferon 1 with point mutations (H1A) A(1)GVSGH(6)GQH(9)GVH(12)G (Allo1A) and (H9A) H(1)GVSGH(6)GQA(9)GVH(12)G (Allo9A) have been studied by potentiometric, UV-visible, CD, EPR spectroscopic and mass spectrometry (MS) methods. To obtain a complete complex speciation different metal-to-ligand molar ratios ranging from 1:1 to 4:1 for Allo1A and to 3:1 for Allo9A were studied. The presence of the His residue in first position of the peptide chain changes the coordination abilities of the Allo9A peptide in comparison to that of the Allo1A. Imidazole-N3 atom of N-terminal His residue of the Allo9A peptide forms stable 6-membered chelate with the terminal amino group. Furthermore, the presence of two additional histidine residues in the Allo9A peptide (H(6),H(12)) leads to the formation of the CuL complex with 4N {NH2,NIm-H(1),NIm-H(6),NIm-H(12)} binding site in wide pH range (5-8). For the Cu(II)-Allo1A system, the results demonstrated that at physiological pH7.4 the predominant complex the CuH-1L consists of the 3N {NH2,N(-),CO,NIm} coordination mode. The inductions of phenoloxidase activity and apoptosis in vivo in Tenebrio molitor cells by the ligands and their copper(II) complexes at pH7.4 were studied. The Allo1A, Allo1K peptides and their copper(II) complexes displayed the lowest hemocytotoxic activity while the most active was the Cu(II)-Allo9A complex formed at pH7.4. The results may suggest that the N-terminal-His(1) and His(6) residues may be more important for their proapoptotic properties in insects than those at positions 9 and 12 in the peptide chain.
authors.affiliation: Faculty of Chemistry, University of Wrocław, 14 Joliot-Curie, 50-383 Wroclaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Matusiak
authors.affiliation: Faculty of Chemistry, University of Wrocław, 14 Joliot-Curie, 50-383 Wroclaw, Poland.
authors.forename: Mariola
authors.initials: M
authors.lastname: Kuczer
authors.affiliation: Departament of Animal Physiology and Development, Institute of Experimental Biology, Adam Mickiewicz University, 89 Umultowska, 61-614 Poznań, Poland.
authors.forename: Elżbieta
authors.initials: E
authors.lastname: Czarniewska
authors.affiliation: Departament of Animal Physiology and Development, Institute of Experimental Biology, Adam Mickiewicz University, 89 Umultowska, 61-614 Poznań, Poland.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Rosiński
authors.affiliation: Faculty of Chemistry, University of Wrocław, 14 Joliot-Curie, 50-383 Wroclaw, Poland. Electronic address: teresa.kowalik-jankowska@chem.uni.wroc.pl.
authors.forename: Teresa
authors.initials: T
authors.lastname: Kowalik-Jankowska
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry* / Q000494:pharmacology; D003300:Copper / Q000737:chemistry*; D004355:Drug Stability; D006321:Heart / Q000187:drug effects; D006434:Hemocytes / Q000187:drug effects / Q000473:pathology; D006639:Histidine / Q000737:chemistry*; D008297:Male; D014442:Monophenol Monooxygenase / Q000096:biosynthesis; D009942:Organometallic Compounds / Q000494:pharmacology*; D010455:Peptides / Q000235:genetics* / Q000494:pharmacology*; D017354:Point Mutation; D013712:Tenebrio / Q000187:drug effects / Q000201:enzymology
chemical_list: C510535:Alloferon; D056831:Coordination Complexes; D009942:Organometallic Compounds; D010455:Peptides; D006639:Histidine; D003300:Copper; D014442:Monophenol Monooxygenase
keywords: Alloferon; Apoptosis; Biological activity; Copper; Mono- and polynuclear complexes