title: The impact of synthetic analogs of histidine on copper(II) and nickel(II) coordination properties to an albumin-like peptide. Possible leads towards new metallodrugs.
abstract: The purpose of our research was to obtain peptidomimetics possessing Cu(II) and Ni(II) binding properties, which would be useful for biomedical applications. In this context we used potentiometry, UV-VIS and CD spectroscopies to characterize the Cu(II) and Ni(II) binding properties of pentapeptide analogs of the N-terminal sequence of histatin 5. The peptides investigated had a general sequence DSXAK-am (am stands for C-terminal amide), with X including His and its three synthetic analogs, (4-thiazolyl)-L-alanine (1), (2-pyridyl)-L-alanine (2), and (pyrazol-1-yl)-L-alanine (3). The heterocyclic nitrogens present in these analogs were significantly more acidic than that of the His imidazole. We found that DSXAK-am peptides were able to bind Cu(II) and Ni(II) and form 4N complexes in a cooperative fashion, with similar affinities. These results indicate that acidic heterocyclic amino acids provide a viable alternative for histidine in peptidomimetics designed for metal ion binding.
authors.affiliation: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a, 02-106 Warsaw, Poland. Electronic address: izawisza@ibb.waw.pl.
authors.forename: Izabela
authors.initials: I
authors.lastname: Zawisza
authors.affiliation: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a, 02-106 Warsaw, Poland.
authors.forename: Mariusz
authors.initials: M
authors.lastname: Mital
authors.affiliation: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a, 02-106 Warsaw, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Polkowska-Nowakowska
authors.affiliation: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a, 02-106 Warsaw, Poland.
authors.forename: Arkadiusz
authors.initials: A
authors.lastname: Bonna
authors.affiliation: Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a, 02-106 Warsaw, Poland. Electronic address: wbal@ibb.waw.pl.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Bal
mesh_terms: D000418:Albumins / Q000737:chemistry; D000595:Amino Acid Sequence; D056831:Coordination Complexes / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D006639:Histidine / Q000031:analogs & derivatives* / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008958:Models, Molecular; D009532:Nickel / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry*; D017433:Protein Structure, Secondary
chemical_list: D000418:Albumins; D056831:Coordination Complexes; D009842:Oligopeptides; D006639:Histidine; D003300:Copper; D009532:Nickel
keywords: Complex formation; Copper(II); Nickel(II); Peptides; Synthetic amino acids