About
31
Publications
966
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
185
Citations
Citations since 2017
Introduction
Wide range of interests: role of copper in Alzheimer Disease, realistic 3D reaction - diffusion simulations, reaction equlibria in nanoscopic systems, creating and validating models from spectroscopic data
Skills and Expertise
Publications
Publications (31)
Alzheimer’s Disease (AD) is one of the most common multifactorial diseases characterized by a range of abnormal molecular processes such as the accumulation of extracellular plaques containing the amyloid‐β (Aβ) peptides and dyshomeostasis of copper in the brain. Herein, we investigate the effect of Cu(II) ions on the aggregation of Aβ1‐40, and Aβ4...
The stochastic nature of chemical reaction and impact of the stochasticity on their evolution is soundly documented. Both theoretical predictions and emerging experimental evidence indicate the influence of stochastic effects on the equi-librium state of association reaction. In this work simple mathematical formulas are introduced to estimate thes...
The intracellular exchangeable Zn(II) is usually measured with synthetic fluorescent zinc sensors. 4',5'-Bis[bis(2-pyridylmethyl)aminomethyl]-2',7'-dichlorofluorescein (Zinpyr-1) is a sensor containing the fluorescein platform and a duplicated chelating unit. Its advantages include brightness and a relatively high affinity for Zn(II), Kd = 0.7 nM....
The mechanism of the chemical synapse has been intensively investigated, but the precise time-course of a neurotransmitter in the synaptic cleft is still to be determined. Many approaches to the study of the neurotransmitter flow can be found in the literature, but in most of them the assumption on the simplified geometry has been made. Our first g...
cis-Urocanic acid, a derivative of histidine, is one of the essential components of human skin. We found that it can bind nickel(ii) ions in a pH-dependent manner, with the dissociation constant in the low millimolar range, as revealed by potentiometry, and confirmed by isothermal titration calorimetry and UV-vis spectroscopy. The binding occurs wi...
Covalent protein kinase inhibitors exploit currently noncatalytic cysteines in the adenosine 5'-triphosphate (ATP)-binding site via electrophiles directly appended to a reversible-inhibitor scaffold. Here, we delineate a path to target solvent-exposed cysteines at a distance >10 Å from an ATP-site-directed core module and produce potent covalent ph...
Background:
The stability of a drug or metabolites in biological matrices is an essential part of bioanalytical method validation, but the justification of its sample size (replicates number) is insufficient. The international guidelines differ in recommended sample size to study stability from no recommendation to at least three quality control s...
Tetrathiolate zinc fingers are potential targets of oxidative assault under cellular stress conditions. We used the synthetic 37-residue peptide representing the tetrathiolate zinc finger domain of the DNA repair protein XPA, acetyl-DYVICEECGKEFMSYLMNHFDLPTCDNCRDADDKHK-amide (XPAzf) as a working model to study the reaction of its Zn(II) complex (Zn...
FluoZin-3 is a popular fluorescent sensor for exchangeable biological Zn(II). We demonstrated that its fluorescence intensity is heavily modulated by competition with cellular low molecular weight ligands (LMWLs) and formation of Zn(FluoZin-3)(LMWL) ternary complexes. Determination of their affinity constants empowered us to model the hypothetical...
The interactions between the Aβ1–40 molecules species and the copper ions (Cu(II)) were intensively investigated due to their potential role in the development of the Alzheimer Disease (AD). The rate and the mechanism of the Cu(II)—Aβ complexes formation determines the aggregation pathway of the Aβ species, starting from smaller but more cytotoxic...
Dimerization without Cu(II).
Average fraction of total Aβ bound as a Aβ2 complex [%].
(PDF)
Resting state.
Average fraction of total Aβ bound as a CuAβ2 complex [%] after 20 s.
(PDF)
Excited state.
Average fraction of total Aβ bound as a CuAβ I conformer [%] after 4ms.
(PDF)
Resting state.
Average fraction of total Aβ bound as a CuAβ I conformer [%] after 4ms.
(PDF)
Excited state.
Average fraction of total Aβ bound as a CuAβ2 complex [%] after 20 s.
(PDF)
Short strong excitation.
Average fraction of total Aβ bound as a CuAβ2 complex [%] after 20 s.
(PDF)
Regular long excitation.
Average fraction of total Aβ bound as a CuAβ2 complex [%] after 20 s.
(PDF)
Seleno-substituted model peptides of copper metallochaperone proteins were analyzed for the metal affinity and in vitro anti-oxidative reactivity. An acyclic MTCXXC (X is any amino acid) reference peptide previously analyzed as a potent inhibitor of ROS production underwent substitution of the cysteine residues with selenocysteine to give two singl...
2-[2-[2-[2-[bis(carboxylatomethyl)amino]-5-methoxyphenoxy]ethoxy]-4-(2,7-difluoro-3-oxido-6-oxo-4a,9a-dihydroxanthen-9-yl)anilino]acetate (FluoZin-3) is used very broadly in life sciences as intra- and extracellular Zn(II) sensor selective for Zn(II) over Co(II), Ca(II) and Mg(II) ions at their physiological concentrations. It has been used for det...
In the light of conflicting reports on the ability of copper(II) complexes of amyloid beta (Aβ) peptides to form ternary complexes with small molecules co-present in the biological milieu, we performed a study of coordination equilibria in the system containing Cu(II) ions, the Aβ1–16 peptide, glutamic acid and 4-(2-hydroxyethyl)-1-piperazineethane...
The effect of position II in the binding sequence of copper metallochaperones, which varies between Thr and His, was investigated through structural analysis and affinity and oxidation kinetic studies of model peptides. A first Cys-Cu(I)-Cys model obtained for the His peptide at acidic and neutral pH, correlated with higher affinity and more rapid...
Poly(ADP-ribose) polymerase 1 (PARP-1) is a key eukaryotic enzyme, catalyzing the NAD+ dependent poly(ADP-ribosyl)ation of protein substrates, crucial for major DNA repair pathways, and involved in other fundamental cellular processes, such as transcription, cell cycle control, and apoptosis. Its ability to bind DNA depends on two CCHC zinc finger...
Nickel is harmful for humans, but molecular mechanisms of its toxicity are far from being fully elucidated. One of such mechanisms may be associated with the Ni(II)-dependent peptide bond hydrolysis, which occurs before Ser/Thr in Ser/Thr-Xaa-His sequences. Human annexins A1, A2, and A8, proteins modulating the immune system, contain several such s...
