A5009218318- Trace Elements in Health
- Prion Diseases and Protein Misfolding
- Alzheimer's disease research and treatments
- Neurological diseases and metabolism
- Parkinson's Disease Mechanisms and Treatments
- Metal complexes synthesis and properties
- Crystallography and molecular interactions
- Drug Transport and Resistance Mechanisms
- Protein Structure and Dynamics
- Chemical Synthesis and Analysis
- Antimicrobial Peptides and Activities
- Cholinesterase and Neurodegenerative Diseases
- Microbial Natural Products and Biosynthesis
- RNA and protein synthesis mechanisms
- Electrochemical Analysis and Applications
- Molecular Sensors and Ion Detection
- Mass Spectrometry Techniques and Applications
- Crystallization and Solubility Studies
- Computational Drug Discovery Methods
- Enzyme-mediated dye degradation
- Neuroscience and Neuropharmacology Research
- Protein Interaction Studies and Fluorescence Analysis
- Metabolomics and Mass Spectrometry Studies
- X-ray Diffraction in Crystallography
- Amino Acid Enzymes and Metabolism
University of Siena
2015-2025
Interuniversity Consortium for Magnetic Resonance
2023-2025
Industriale Chimica (Italy)
2019
University of Wrocław
2002-2009
University of Gdańsk
2005-2008
University of Ferrara
2004
Istituto di Metodologie Chimiche
1999-2000
University of Pisa
2000
The aggregation of alpha-synuclein (AS) is a critical step in the etiology Parkinson's disease (PD). A central, unresolved question pathophysiology PD relates to role AS-metal interactions amyloid fibril formation and neurodegeneration. Our previous works established hierarchy alpha-synuclein-metal ion interactions, where Cu(II) binds specifically protein triggers its under conditions that might be relevant for development PD. Two independent, non-interacting copper-binding sites were...
The synthetic peptide encompassing residues 106−126 (PrP106−126, KTNMKHMAGAAAAGAVVGGLG) of the human prion protein was considered for its binding properties toward copper(II), manganese(II) and zinc(II) at pH 5.7. 1H 13C 1D spectra, spin−lattice relaxation rates, 1H−15N 1H−13C HSQC 2D experiments were obtained in absence presence metal ions. While Zn(II) found to yield negligible effects upon any NMR parameter, metal−peptide association demonstrated by paramagnetic Cu(II) Mn(II) spectra....
Alzheimer's disease is a fatal neurodegenerative disorder involving the abnormal accumulation and deposition of peptides (amyloid-β, Aβ) derived from amyloid precursor protein. Here, we present structure Zn2+ binding sites human rat Aβ(1−28) fragments in water/sodium dodecyl sulfate (SDS) micelles by using 1H NMR spectroscopy. The chemical shift variations measured after addition at T > 310 K allowed us to assign donor atoms both zinc complexes. Asp-1 amine, His-6 Nδ, Glu-11 COO-, His-13 Nε...
The reaction of the ruthenium(II) complex fac-[Ru(CO)(3)Cl(2)(N(1)-thz)] (I hereafter; thz = 1,3-thiazole) with human beta-amyloid peptide 1-28 (Abeta(28)) and resulting {Ru(CO)(3)}(2+) adduct was investigated by a variety biophysical methods. (1)H NMR titrations highlighted selective interaction Abeta(28) histidine residues; circular dichroism revealed occurrence substantial conformational rearrangement Abeta(28); electrospray ionization mass spectrometry (ESI-MS) suggested prevalent 1:1...
The aggregation of α-synuclein (αS) is a critical step in the etiology Parkinson's disease. Metal ions such as copper and iron have been shown to bind αS, enhancing its fibrillation rate vitro. αS also susceptible copper-catalyzed oxidation that involves reduction CuII CuI conversion O2 into reactive oxygen species. mechanism reaction highly selective site-specific interactions protein with both states ion. can induce oxidative modification protein, which generally leads extensive...
Plants have evolved a set of mechanisms that control and respond to the uptake accumulation both essential non-essential metals, including chelation sequestration these elements by thiol ligands, such as glutathione phytochelatins. Indeed, peptides can chelate some quickly form thiol-metal complexes, segregate them in vacuolar compartment. Reasonably, conceptually similar be assumed responsible for transport metal complexes ̶ particular thiol-cadmium across plasma membrane, with consequent...
PvHCt, a 23-amino acid long, histidine-rich peptide derived from shrimp, becomes strongly antimicrobial upon Cu(ii) ion binding. We describe Zn(ii) and complexes of this peptide, aiming to understand how metal binding structure correlates biological activity. Using NMR, UV-vis, CD FTIR spectroscopies, along with cyclic voltammetry, potentiometry, DFT calculations, we demonstrate that binds the central C-terminal regions inducing significant structural changes. These include pronounced bend...
The mechanisms of Cu import across the bacterial outer membrane have been investigated only in a few cases. One such mechanism involves OprC transporter with unique CxxxM-HxM metal-binding site, discovered recently. This newly identified site is located outside cell and is, therefore, most likely to bind Cu(II) through this domain. Since may interact azurin facilitate removal copper, our study potential role CopM metallophore. We selected two putative sites CopM, characterized by MxxHH MHxxH...
Fragments of MUC7, a salivary protein involved in nonimmune defense, arise from proteolytic cleavage saliva and exhibit antimicrobial properties. However, their therapeutic use is limited by low stability due to further degradation. To address this, native MUC7 fragment was modified using d-amino acids the retro-inverso strategy. Given role metal ions enhancing peptides, we analyzed bioinorganic chemistry these systems with Cu(II) assessed activity against fungal bacterial strains. This...
Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder characterized by metabolic dysregulation, oxidative stress, amyloid-β (Aβ) aggregation, metal dyshomeostasis, and mitochondrial dysfunction. Current treatments provide only symptomatic relief, highlighting the need for novel therapeutic strategies. This study investigates effects of alkaloids galantamine (GAL) lycorine (LYC) in differentiated SH-SY5Y neuroblastoma cells, an established vitro model AD, which acquire...
Potentiometric and spectroscopic data have shown that octarepeat dimer tetramer are much more effective ligands for Cu(II) ions than simple octapeptide. Thus, the whole N-terminal segment of prion protein due to cooperative effects, could be in binding peptides containing a His residue. The gain by longer derives from involvement up four imidazoles coordination first ion. This type increases order peptide structure, which allows successive metal easier coordination.
Ac-PHGGGWGQ-NH2, an octarepeat peptide fragment of prion, is a relatively effective ligand for Cu2+ ions. At pH about 7.4 the major binding sites involve imidazole nitrogen and two amide nitrogens 3Gly 4Gly giving CuH−2L species. The stability complex formed similar to other peptides having type coordination. NMR spectra indicate that in side chain Trp residue located very close metal ion. geometry around ion seems be slightly distorted from tetragonal one. In strongly basic solution...
The mechanism of membrane permeabilization by dermcidin (DCD-1L), an antimicrobial peptide present in human sweat, was investigated at a mercury-supported monolayer dioleoylphosphatidylcholine (DOPC) or dioleoylphosphatidylserine (DOPS) and tethered bilayer lipid (tBLM) consisting thiolipid (DPTL) with DOPC DOPS self-assembled on top it. In unbuffered solution pH 5.4, DCD-1L is almost neutral permeabilizes DPTL/DOPS tBLM transmembrane potentials, ϕtrans, which are physiological. 7 buffer...
Parkinson's disease (PD) is a neurodegenerative disorder characterized by the presence of abnormal α-synuclein (αSyn) deposits in brain. Alterations metal homeostasis and metal-induced oxidative stress may play crucial role aggregation αSyn and, consequently, pathogenesis PD. We have therefore investigated capability copper-αSyn6 copper-αSyn15 peptide complexes, with 1-6 1-15 terminal fragments protein, to promote redox reactions that can be harmful other cellular components. The...
Tau protein is present in significant amounts neurons, where it contributes to the stabilization of microtubules. Insoluble neurofibrillary tangles tau are associated with several neurological disorders known as tauopathies, among which Alzheimer's disease. In binds tubulin through its microtubule binding domain comprises four imperfect repeats (R1-R4). The histidine residues contained these fragments potential sites for metal ions and located close regions that drive formation amyloid...