Publications by authors named "Olga Iranzo"

Article Synopsis
  • Metal-based chemotherapeutics, particularly cisplatin, are commonly used for cancer treatment, but researchers are exploring alternatives like copper (Cu) complexes to reduce side effects.
  • A study focused on enhancing a Cu(II) compound known for its ability to generate reactive oxygen species (ROS), by adding functional groups that improve solubility and cellular uptake without altering its core redox activity.
  • Results showed that while some modifications didn't enhance cytotoxicity, using cell-penetrating peptides significantly improved the anticancer effectiveness of the Cu(II) complex and ensured better delivery into cells, suggesting potential strategies for developing more effective cancer treatments.
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Three novel dinuclear Cu(II) complexes based on a ,,-chelating salphen-like ligand scaffold and bearing varying aromatic substituents (-H, -Cl, and -Br) have been synthesized and characterized. The experimental and computational data obtained suggest that all three complexes exist in the dimeric form in the solid state and adopt the same conformation. The mass spectrometry and electron paramagnetic resonance results indicate that the dimeric structure coexists with the monomeric form in solution upon solvent (dimethyl sulfoxide and water) coordination.

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Article Synopsis
  • Researchers successfully synthesized 3,4-Dimercaptophenylalanines and 2,3-Dimercaptophenylalanines for the first time using nucleophilic substitution techniques.
  • The key steps involved protecting dithiol functions as thioketals and synthesizing intermediates from dihydroxy benzoates or toluene-3,4-dithiol.
  • The study concluded that this simple synthetic method allows for the production of dithiolene-functionalized peptides, which have potential applications in catalysis, diagnostics, and nanotechnology.
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Cu, Zn, and amyloid-β (Aβ) peptides play an important role in the etiology of Alzheimer's disease (AD). Their interaction indeed modifies the self-assembly propensity of the peptide that is at the origin of the deposition of insoluble peptide aggregates in the amyloid plaque, a hallmark found in AD brains. Another even more important fallout of the Cu binding to Aβ peptide is the formation of reactive oxygen species (ROS) that contributes to the overall oxidative stress detected in the disease and is due to the redox ability of the Cu ions.

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De Novo metalloprotein design assesses the relationship between metal active site architecture and catalytic reactivity. Herein, we use an α-helical scaffold to control the iron coordination geometry when a heme cofactor is allowed to bind to either histidine or cysteine ligands, within a single artificial protein. Consequently, we uncovered a reversible pH-induced switch of the heme axial ligation within this simplified scaffold.

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The emergence of superbugs developing resistance to antibiotics and the resurgence of microbial infections have led scientists to start an antimicrobial arms race. In this context, we have previously identified an active RiPP, the Ruminococcin C1, naturally produced by E1, a symbiont of the healthy human intestinal microbiota. This RiPP, subclassified as a sactipeptide, requires the host digestive system to become active against pathogenic Clostridia and multidrug-resistant strains.

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Competitive Cu(II)-binding studies have been carried out between five decapeptides (both acyclic and cyclic), namely , , , and , and the Aβ(1-16) and Aβ(1-40) fragments. Conformational constraints in such peptidic scaffolds affect their copper-binding affinity, which can be tuned. In the present study, the ability of these peptides to compete with Aβ has been assessed , with the objective to examine whether such soft chelating agents may be used to lessen the deleterious interaction of Cu(II) with Aβ.

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Superoxide dismutases (SODs) are highly efficient enzymes for superoxide dismutation and the first line of defense against oxidative stress. These metalloproteins contain a redox-active metal ion in their active site (Mn, Cu, Fe, Ni) with a tightly controlled reduction potential found in a close range around the optimal value of 0.36 V versus the normal hydrogen electrode (NHE).

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A major public health challenge today is the resurgence of microbial infections caused by multidrug-resistant strains. Consequently, novel antimicrobial molecules are actively sought for development. In this context, the human gut microbiome is an under-explored potential trove of valuable natural molecules, such as the ribosomally-synthesized and post-translationally modified peptides (RiPPs).

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Article Synopsis
  • The study focuses on how certain copper (Cu(II)/Cu(I)) complexes can generate reactive oxygen species (ROS), which may help induce cancer cell death.
  • Researchers synthesized and characterized four existing Cu(II) complexes with N-donor ligands, originally designed for different purposes, to explore their potential as anticancer agents.
  • The investigation includes assessing the complexes' abilities to interact with DNA, generate ROS, and the role of ligands, indicating that reusing these "old" complexes could lead to novel and effective cancer treatments.
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N-Methylation of the peptide amide bond has proven to be a powerful strategy to fine-tune the conformation and properties of peptides. In this context and for the first time, we show that N-methylation can also be used to control the copper(ii) coordination properties of peptides and stabilize at high pH values the copper(ii) species lacking amidate coordination. Namely, we have prepared a derivative of the O-Asp peptide where the copper(ii) coordinating amino acids, i.

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E-selectin is overexpressed on angiogenic and inflamed endothelium. Molecules binding to E-selectin with high affinity and specificity enable its use as a molecular imaging biomarker. The interactions of four different peptides (i.

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Water oxidation by copper-based complexes to form dioxygen has attracted attention in recent years, with the aim of developing efficient and cheap catalysts for chemical energy storage. In addition, high-valent metal-oxo species produced by the oxidation of metal complexes in the presence of water can be used to achieve substrate oxygenation with the use of H O as an oxygen source. To date, this strategy has not been reported for copper complexes.

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Extracellular hemoglobin, a byproduct of hemolysis, can release its prosthetic heme groups upon oxidation. This produces metabolically active heme that is exchangeable between acceptor proteins, macromolecules and low molecular weight ligands, termed here labile heme. As it accumulates in plasma labile heme acts in a pro-oxidant manner and regulates cellular metabolism while exerting pro-inflammatory and cytotoxic effects that foster the pathogenesis of hemolytic diseases.

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A new triethylbenzene-derived tetraazamacrocycle containing pyridyl spacers, L, was prepared and its dinuclear copper(ii) complex was used as a receptor for the recognition of phosphorylated peptides in aqueous solution. A detailed study of the acid-base behaviour of L and its copper(ii) complexation properties as well as of the cascade species with phosphorylated anions including two peptidic substrates was carried out in a HO/MeOH (50 : 50 v/v) solution using different techniques, such as potentiometry, X-band EPR and DFT calculations. The association constants of the dinuclear receptor with the phosphorylated peptides and other anionic species revealed a clear preference towards phenylic phosphorylated substrates, with values ranging 3.

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Microbubbles (MB) are routinely used as contrast agents for ultrasound (US) imaging. We describe different types of targeted and drug-loaded poly(n-butyl cyanoacrylate) (PBCA) MB, and demonstrate their suitability for multiple biomedical applications, including molecular US imaging and US-mediated drug delivery. Molecular imaging of angiogenic tumor blood vessels and inflamed atherosclerotic endothelium is performed by modifying the surface of PBCA MB with peptides and antibodies recognizing E-selectin and VCAM-1.

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Copper(II) complexes have been intensely investigated in a variety of diseases and pathological conditions due to their therapeutic potential. The development of these complexes requires a good knowledge of metal coordination chemistry and ligand design to control species distribution in solution and tailor the copper(II) centers in the right environment for the desired biological activity. Herein we present the synthesis and characterization of two ligands HL1 and HL2 containing a phenanthroline unit (phen) attached to the amino group of histidine (His).

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Recent advances in de novo protein design have gained considerable insight from the intrinsic dynamics of proteins, based on the integration of molecular dynamics simulations protocols on the state-of-the-art de novo protein design protocols used nowadays. With this protocol we illustrate how to set up and run a molecular dynamics simulation followed by a functional protein dynamics analysis. New users will be introduced to some useful open-source computational tools, including the GROMACS molecular dynamics simulation software package and ProDy for protein structural dynamics analysis.

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The cyclic decapeptide C-Asp, containing one Asp residue and three His residues, was designed by Fragoso et al. (Chem. Eur.

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The reactive species of oxygen and chlorine damage cellular components, potentially leading to cell death. In proteins, the sulfur-containing amino acid methionine is converted to methionine sulfoxide, which can cause a loss of biological activity. To rescue proteins with methionine sulfoxide residues, living cells express methionine sulfoxide reductases (Msrs) in most subcellular compartments, including the cytosol, mitochondria and chloroplasts.

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Metalloproteases have evolved in a vast number of biological systems, being one of the most diverse types of proteases and presenting a wide range of folds and catalytic metal ions. Given the increasing understanding of protein internal dynamics and its role in enzyme function, we are interested in assessing how the structural heterogeneity of metalloproteases translates into their dynamics. Therefore, the dynamical profile of the clan MA type protein thermolysin, derived from an Elastic Network Model of protein structure, was evaluated against those obtained from a set of experimental structures and molecular dynamics simulation trajectories.

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Purpose: Our objective was to determine the lowest diagnostically effective dose for E-selectin-targeted poly n-butyl cyanoacrylate (PBCA)-shelled microbubbles and to apply it to monitor antiangiogenic therapy effects.

Procedures: PBCA-shelled microbubbles (MBs) coupled to an E-selectin-specific peptide were applied in mice carrying MLS or A431 carcinoma xenografts scaling down the MB dosage to the lowest level where binding could be examined with a 18-MHz small animal ultrasound transducer. Differences in E-selectin expression in the two carcinoma xenografts were confirmed by enzyme-linked immunosorbent assay (ELISA).

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A linear decapeptide containing three His and one Asp residues and a β-turn-inducing dProPro unit was synthesised. A detailed potentiometric, mass spectrometric and spectroscopic study showed that at a 1:1 ratio of CCu /Cpeptide this peptide formed a major [CuH(O(dPro)-Asp)](2+) species (pH range 5.5-7.

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Alzheimer's disease is a grave social problem in an aging population. A major problem is the passage of drugs through the blood-brain barrier. This work tests the hypothesis that the conjugation of peptidomimetic β-secretase inhibitors with a fragment of amyloid-β peptide facilitates entrance into the central nervous system.

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