1,844 research outputs found
De Novo Designed Copper α-Helical Peptides: From Design to Function
Full text linkDe novo protein design is a fascinating and powerful approach to the design of metal sites in the interior of simplified protein scaffolds. A series of de novo designed copper peptides are herein described. They consist of peptide constructs that possess a secondary and tertiary structure, and that can be regarded as simplified proteins from which most of the structural complexity has been removed. Although relatively small, these copper peptides retain enough complexity to show features typical of proteins, such as enzyme-like catalytic behavior or specific spectroscopic features. This review focuses on the de novo design of α-helical constructs and in their use to devise different types of copper centers. Through the proper design of the peptide sequences, it has been possible to study the Cu-triggered folding of peptide strands, which resulted in the isolation of enzyme regulators and biosensors for copper. Moreover, the use of Cys-containing peptides allowed us to design sites structurally similar to the copper-binding sites of biomolecules involved in copper trafficking and homeostasis. Finally, catalytic copper Type 2 sites capable of undergoing redox reactions and copper Type 1 and Type A centers with spectroscopic characteristics remarkably similar to those of natural proteins are discussed
Metallacrowns of copper(II) and aminohydroxamates: Thermodynamics of self assembly and host–guest equilibria
No full textMetallacrowns (MCs) of copper(II) and aminohydroxamic acids have been extensively studied during the past few decades. Although their discovery dates back more than twenty years, systematic studies on the thermodynamics of self assembly of MCs and of their capability to act as guests for anions and cations are quite recent. This review focuses on the solution studies of these metallamacrocycles and, in particular, the following aspects are discussed: (i) the thermodynamics of self-assembly of 12-MC-4 complexes; (ii) the thermodynamics of self-assembly and core metal substitution of 15-MC-5 species; (iii) the thermodynamics of host–guest equilibria between 15-MC-5 complexes and anions. The overall thermodynamic parameters for the formation of a wide number of 12-MC-4 species of α-, β- and γ-aminohydroxamates are discussed together with the most relevant structural, spectroscopic and reactivity features reported in the literature for copper(II) metallacrowns. These data provide a thermodynamic quantitation of the “metallacrowns structural paradigm”, and show the possibility to devise new MCs with desired stabilities in different medium conditions through an appropriate choice of metal coordinating moieties and ligand dimensions. The thermodynamics of self-assembly of 15-MC-5 is discussed for Ca2+ and Ln3+ as core metals, and the overall formation constants are used to evaluate the copious literature data regarding the stability of these species in solution. The relative stability of 15-MC-5 complexes of different Ln3+ ions is also discussed, showing the extraordinary capability of these complexes to discriminate different Ln3+ ions on the basis of their dimensions. Finally, the thermodynamics of host–guest equilibria of 15-MC-5 complexes as receptors for carboxylates is presented: the binding affinities of different carboxylates for the 15-MC-5 species with Ln3+ as the core metal are discussed on the basis of guests hydrophobicity, dimension and basicity, and in terms of core metal Lewis acidity
Aspects of NMR Characterization of Metallacrowns
No full textMetallacrowns (MCs) are self-assembled metallamacrocycles that confine a significant number of metal ions and organic ligands in a small molecular volume. These assembled structures present a cavity that can selectively encapsulate specific metal ions which provide MCs with peculiar spectroscopic features and reactivity. Also, MCs can bind inorganic and organic anions allowing their use in strategies of molecular recognition. For these reasons, including remarkable stability and inertness toward disassembly and the presence of paramagnetic ions in their structure, MCs possibly are among the most interesting metallamacrocyclic complexes known to date. The elucidation of dynamic processes of ligand and solvent exchange in solution is pivotal in the study of MCs as potential probes in biological imaging, as nanoshuttles for drug delivery or in molecular recognition and sensing. In this chapter, we will present and discuss representative examples of NMR investigations of metallacrowns reactivity, dynamics of assembly, and cations/anions binding. The strategies and conditions employed in the 1D NMR characterization of MCs will be discussed along with the most recent PGSE approaches. Also, we will discuss how the paramagnetic nature of these complexes opens a window into the study of their structure in solution through NMR
Speciation and structure of copper(II) complexes with (S)-phenylalanine- and (S)-tryptophanhydroxamic acids in methanol/water solution: a combined potentiometric, spectrophotometric, CD and ESI-MS study
No full textSuccinylhydroxamic derivatives of α-amino acids as MMP inhibitors. Study of complex-formation equilibria with Cu2+, Ni2+ and Zn2+
No full textRevisiting the significance of kinetic inertia in complex formation/decomplexation of metal–ATCUN peptide complexes
No full textResearch on copper and nickel complexes formed by an amino terminal Cu(II) and Ni(II) binding (ATCUN) motif has greatly progressed in recent decades. These compounds are of considerable interest in bioinorganic chemistry, both as potential metallodrug candidates and as artificial metalloenzymes. Although the high stability of the Cu(II)- and Ni(II)-ATCUN complexes under physiologically relevant conditions is well established, the kinetic inertia associated with their formation has often been underestimated, particularly in the context of their catalytic applications. Here, we prepared ATCUN peptides (GGHWGKRG-Am; GGH-Pep) and investigated the stability of their Cu(II) and Ni(II)-ATCUN complexes in aqueous solutions under conditions enabling 1 : 1 metal-to-peptide complex formation at micromolar concentrations. Systematic pH titration revealed that the low basicity of the N-terminal amine of the peptide contributes to stabilizing the metal-ATCUN complex in aqueous solution. These findings highlight the need to account for kinetic inertia when evaluating ATCUN-like complexes under catalytically relevant conditions
Copper chelators: chemical properties and bio-medical applications
No full textCopper is present in different concentrations and chemical forms throughout the earth crust, surface and deep water and even, in trace amounts, in the atmosphere itself. Copper is one of the first metals used by humans, the first artifacts dating back 10,000 years ago. Currently, the world production of refined copper exceeds 16,000 tons/year. Copper is a micro-element essential to life, principally for its red-ox properties that make it a necessary cofactor for many enzymes, like cytochrome-c oxidase and superoxide dismutase. In some animal species (e.g. octopus, snails, spiders, oysters) copper-hemocyanins also act as carriers of oxygen instead of hemoglobin. However, these red-ox properties also make the pair Cu(+)/Cu(2+) a formidable catalyst for the formation of reactive oxygen species, when copper is present in excess in the body or in tissues. The treatment of choice in cases of copper overloading or intoxication is the chelation therapy. Different molecules are already in clinical use as chelators or under study or clinical trial. It is worth noting that chelation therapy has also been suggested to treat some neurodegenerative diseases or cardiovascular disorders. In this review, after a brief description of the homeostasis and some cases of dyshomeostasis of copper, the main (used or potential) chelators are described; their properties in solution, even in relation to the presence of metal or ligand competitors, under physiological conditions, are discussed. The legislation of the most important Western countries, regarding both the use of chelating agents and the limits of copper in foods, drugs and cosmetics, is also outlined
Thermodynamics of binding of carboxylates to amphiphilic Eu(3+)/Cu(2+) metallacrown.
No full textThe binding constants of acetate and benzoate to a Pheha-based 15-metallacrown-5 have been determined by a fluorimetric indicator displacement assay demonstrating on a thermodynamic basis the stabilization effect arising from complexation of the less polar carboxylate into the hydrophobic pocket of the metallacrown scaffold
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