title: Copper(II) complexes of neurokinin A with point mutation (S5A) and products of copper-catalyzed oxidation; role of serine residue in peptides containing neurokinin A sequence.
abstract: A potentiometric, spectroscopic (UV-visible, CD and EPR) and electrospray ionization mass spectrometric (ESI-MS) study of Cu(II) binding to the neurokinin A with point mutation (S5A) (ANKA), His-Lys-Thr-Asp-Ala(5)-Phe-Val-Gly-Leu-Met-NH2 and its N-acethyl derivative (Ac-ANKA), Ac-His-Lys-Thr-Asp-Ala(5)-Phe-Val-Gly-Leu-Met-NH2 were carried out. For the ANKA and Ac-ANKA the additional deprotonation was not observed. It suggests that for the tachykinin peptides with C-terminal sequence of neurokinin A for the additional deprotonation the presence of the serine residue is necessary. For the Cu(II)-ANKA 1:2 system at physiological pH 7.4 the CuH2L2 species is present with histamine-like 4N, 2×{NH2,NIm} coordination mode. With increasing pH the deprotonation and coordination of amide nitrogen atoms occur and the CuH-2L, CuH-3L complexes are formed. In pH range 4.5 - 9.5 the dimeric Cu2HL2, Cu2L2 and Cu2H-1L2 species in solution are also present. To elucidate the products of the copper(II)- catalyzed oxidation of the ANKA and Ac-ANKA, the liquid chromatography-mass spectrometry (LC-MS) method and Cu(II)/hydrogen peroxide as a model oxidizing system were employed. In the presence of hydrogen peroxide with 1:1 peptide-H2O2 molar ratio for both peptides the oxidation of the methionine residue to methionine sulfoxide was observed. For the Cu(II)-peptide-hydrogen peroxide in 1:2:2 molar ratio systems oxidations of the histidine residues to 2-oxo-histidines and methionine sulfoxide to methionine sulfone were detected.
authors: Faculty of Chemistry, University of Gdańsk, Sobieskiego 18, 80-952 Gdańsk, Poland.
authors: Elżbieta
authors: E
authors: Jankowska
authors: Marta
authors: M
authors: Błaszak
authors: Teresa
authors: T
authors: Kowalik-Jankowska
mesh_terms: D000409:Alanine / Q000737:chemistry* / Q000235:genetics; D000818:Animals; D002853:Chromatography, Liquid; D056831:Coordination Complexes / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D006639:Histidine / Q000737:chemistry; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry; D007700:Kinetics; D013058:Mass Spectrometry; D008715:Methionine / Q000031:analogs & derivatives / Q000737:chemistry; D015288:Neurokinin A / Q000138:chemical synthesis / Q000737:chemistry* / Q000235:genetics; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000235:genetics; D010084:Oxidation-Reduction; D017354:Point Mutation; D011522:Protons; D012694:Serine / Q000737:chemistry* / Q000235:genetics
chemical_list: D056831:Coordination Complexes; D009842:Oligopeptides; D011522:Protons; C018332:methionine sulfone; D012694:Serine; D006639:Histidine; D003300:Copper; D015288:Neurokinin A; D008715:Methionine; D006861:Hydrogen Peroxide; D000409:Alanine; C013111:methionine sulfoxide