Keywords: Alkaline Conditions, Anchoring Groups, Coordinating Donors, Coordination Modes, Copper (ii), Copper Complexes, Copper Ions, Data Support, Density Functional Theory Calculations, Deprotonated Amides, Metal Binding, Metal Binding Ligands, Ph Range, Physiological Condition, Physiological Ph Range, Polar Side Chains, Side-Chains, Specific Sequences, Spectral Parameters, Spectroscopic Method, Tetra Peptide, Alkalinity, Amino Acids, Electron Spin Resonance Spectroscopy, Spectroscopic Analysis, Stoichiometry, Copper Compounds, Amylin, Organometallic Compound, Amino Acid Sequence, Animal, Article, Chemical Structure, Chemistry, Human, Molecular Genetics, Quantum Theory, Synthesis, Islet Amyloid Polypeptide, Molecular Sequence Data, Molecular Structure,
Affiliations: *** IBB - CNR ***
Department of Inorganic and Analytical Chemistry, University of Debrecen, Hungary. email@example.com
CNR Institute of Biomolecular Chemistry, Traversa La Crucca 3, 07040, Baldinca-Li Punti (Sassari), Italy
Department of Chemistry, Center for Biotechnology Development and Biodiversity Research, University of Sassari, Via Vienna 2, 07100, Sassari, Italy
Department of Pharmaceutical Sciences, University of Connecticut, Unit 3092, 69 North Eagleville Rd, Storrs, CT 06269, United States
References: Not available.
Copper(II) complexes of rat amylin fragments
The fragments of rat amylin rIAPP(17-29) (Ac-VRSSNNLGPVLPP-NH(2)), rIAPP(17-22) (Ac-VRSSNN-NH(2)), rIAPP(19-22) (Ac-SSNN-NH(2)) and rIAPP(17-20) (Ac-VRSS-NH(2)) together with the related mutant peptides (Ac-VASS-NH(2) and Ac-VRAA-NH(2)) have been synthesized and their copper(II) complexes studied by potentiometric, UV-Vis, CD and EPR spectroscopic methods. Despite the lack of any common strongly coordinating donor functions some of these fragments are able to bind copper(II) ions in the physiological pH range. The longest fragment rat amylin(17-29) keeps one equivalent copper(II) ion in solution in the whole pH range, while two other peptides Ac-VRSSNN-NH(2) and Ac-SSNN-NH(2) are also able to interact with copper(II) ions in the slightly alkaline pH range. According to the spectral parameters of the complexes, the peptides can be classified into two different categories: (i) the tetrapeptides Ac-VRSS-NH(2), Ac-VASS-NH(2) and Ac-VRAA-NH(2) can interact with copper(II) only under strongly alkaline conditions (pH > 10.0) and the formation of only one species with four amide nitrogen coordination can be detected; (ii) the peptides Ac-VRSSNNLGPVLPP-NH(2), Ac-VRSSNN-NH(2) and Ac-SSNN-NH(2) can form complexes above pH 6.0 with the major stoichiometries [CuH(-2)L], [CuH(-3)L](-) and [CuH(-4)L](2-). These data support that rIAPP(17-29) can interact with copper(II) ions under physiological conditions and the SSNN tetrapeptide fragment can be considered as the shortest sequence responsible for metal binding. Density functional theory (DFT) calculations provide some information on the possible coordination modes of Ac-SSNN-NH(2) towards the copper(II) ion and suggest that for [CuH(-2)L], [CuH(-3)L](-) and [CuH(-4)L](2-), the binding of two, three and four deprotonated amide nitrogens, with NH(-) of the side chain of asparagine as anchoring group, is probable. Moreover, these data reveal that peptides can be effective metal binding ligands even in the absence of anchoring groups, if more polar side chains are present in a specific sequence.