title: The copper(II) coordination abilities of three novel cyclic tetrapeptides with -His-Xaa-His- motif.
abstract: Three novel cyclic tetrapeptides, containing either l- or d-histidine residues and either Lys or Asp side chains, namely c(HGd-HK) (1), cHGHD (2) and c(HGd-HD) (3), were designed, synthesized, characterized and tested as potential copper(II) ligands. Their pH dependent copper(II) binding properties were analysed in depth by a number of potentiometric and spectroscopic determinations. A rather exhaustive description of the species existing in solution has emerged for each copper(II)/oligopeptide system; solution structures for the individual species are proposed. The specific role of the various side chains in the overall metal coordination process is discussed in comparison with the case of Cu(II)-c(HGHK), previously reported. Data obtained in this study highlight the strong impact of the d-His residue on the metal binding abilities of these cyclic peptides. Remarkably, the cyclic tetrapeptides containing two l-His residues are able to form, at physiologically relevant pH values, a characteristic chromophore where the mononuclear copper(II) centre is simultaneously coordinated by two imidazole nitrogens and two amidic nitrogens of the tetrazadodecane ring. This latter type of copper(II) chromophore has been carefully modelled by computational methods. The potentialities of the applied experimental strategy are stressed.
authors.affiliation: Department of Inorganic Chemistry, Wrocław Medical University, Szewska 38, 50-139 Wrocław, Poland.
authors.forename: Justyna
authors.initials: J
authors.lastname: Brasuń
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Matera
authors.forename: Stanisław
authors.initials: S
authors.lastname: Ołdziej
authors.forename: Jolanta
authors.initials: J
authors.lastname: Swiatek-Kozłowska
authors.forename: Luigi
authors.initials: L
authors.lastname: Messori
authors.forename: Chiara
authors.initials: C
authors.lastname: Gabbiani
authors.forename: Marco
authors.initials: M
authors.lastname: Orfei
authors.forename: Mauro
authors.initials: M
authors.lastname: Ginanneschi
mesh_terms: D001665:Binding Sites; D002942:Circular Dichroism; D003198:Computer Simulation; D003300:Copper / Q000737:chemistry*; D006639:Histidine / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D015394:Molecular Structure; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D011199:Potentiometry; D021241:Spectrometry, Mass, Electrospray Ionization; D013329:Structure-Activity Relationship
chemical_list: D010446:Peptide Fragments; D006639:Histidine; D003300:Copper