Look at a list of IC publications: 2022, 2021, 2020, 2019, 2018, 2017, 2016, 2015, 2014
2022
Lamba, Doriano; Pesaresi, Alessandro
In: International Journal of Molecular Sciences, vol. 23, no. 9, pp. 5072, 2022, ISSN: 1422-0067.
@article{ijms23095072,
title = {Kinetic Modeling of Time-Dependent Enzyme Inhibition by Pre-Steady-State Analysis of Progress Curves: The Case Study of the Anti-Alzheimer\’s Drug Galantamine},
author = {Doriano Lamba and Alessandro Pesaresi},
doi = {10.3390/ijms23095072},
issn = {1422-0067},
year = {2022},
date = {2022-05-03},
urldate = {2022-01-01},
journal = {International Journal of Molecular Sciences},
volume = {23},
number = {9},
pages = {5072},
abstract = {The Michaelis-Menten model of enzyme kinetic assumes the free ligand approximation, the steady-state approximation and the rapid equilibrium approximation. Analytical methods to model slow-binding inhibitors by the analysis of initial velocities have been developed but, due to their inherent complexity, they are seldom employed. In order to circumvent the complications that arise from the violation of the rapid equilibrium assumption, inhibition is commonly evaluated by pre-incubating the enzyme and the inhibitors so that, even for slow inhibitors, the binding equilibrium is established before the reaction is started. Here, we show that for long drug-target residence time inhibitors, the conventional analysis of initial velocities by the linear regression of double-reciprocal plots fails to provide a correct description of the inhibition mechanism. As a case study, the inhibition of acetylcholinesterase by galantamine, a drug approved for the symptomatic treatment of Alzheimer\’s disease, is reported. For over 50 years, analysis based on the conventional steady-state model has overlooked the time-dependent nature of galantamine inhibition, leading to an erroneous assessment of the drug potency and, hence, to discrepancies between biochemical data and the pharmacological evidence. Re-examination of acetylcholinesterase inhibition by pre-steady state analysis of the reaction progress curves showed that the potency of galantamine has indeed been underestimated by a factor of ~100.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The Michaelis–Menten model of enzyme kinetic assumes the free ligand approximation, the steady-state approximation and the rapid equilibrium approximation. Analytical methods to model slow-binding inhibitors by the analysis of initial velocities have been developed but, due to their inherent complexity, they are seldom employed. In order to circumvent the complications that arise from the violation of the rapid equilibrium assumption, inhibition is commonly evaluated by pre-incubating the enzyme and the inhibitors so that, even for slow inhibitors, the binding equilibrium is established before the reaction is started. Here, we show that for long drug-target residence time inhibitors, the conventional analysis of initial velocities by the linear regression of double-reciprocal plots fails to provide a correct description of the inhibition mechanism. As a case study, the inhibition of acetylcholinesterase by galantamine, a drug approved for the symptomatic treatment of Alzheimer’s disease, is reported. For over 50 years, analysis based on the conventional steady-state model has overlooked the time-dependent nature of galantamine inhibition, leading to an erroneous assessment of the drug potency and, hence, to discrepancies between biochemical data and the pharmacological evidence. Re-examination of acetylcholinesterase inhibition by pre-steady state analysis of the reaction progress curves showed that the potency of galantamine has indeed been underestimated by a factor of ~100.
Ferreri, Carla; Sansone, Anna; Krokidis, Marios G.; Masi, Annalisa; Pascucci, Barbara; D’Errico, Mariarosaria; Chatgilialoglu, Chryssostomos
Effects of Oxygen Tension for Membrane Lipidome Remodeling of Cockayne Syndrome Cell Models Journal Article
In: Cells, vol. 11, no. 8, 2022, ISSN: 2073-4409.
@article{cells11081286,
title = {Effects of Oxygen Tension for Membrane Lipidome Remodeling of Cockayne Syndrome Cell Models},
author = {Carla Ferreri and Anna Sansone and Marios G. Krokidis and Annalisa Masi and Barbara Pascucci and Mariarosaria D’Errico and Chryssostomos Chatgilialoglu},
url = {https://www.mdpi.com/2073-4409/11/8/1286},
doi = {10.3390/cells11081286},
issn = {2073-4409},
year = {2022},
date = {2022-04-10},
urldate = {2022-01-01},
journal = {Cells},
volume = {11},
number = {8},
abstract = {Oxygen is important for lipid metabolism, being involved in both enzymatic transformations and oxidative reactivity, and is particularly influent when genetic diseases impair the repair machinery of the cells, such as described for Cockayne syndrome (CS). We used two cellular models of transformed fibroblasts defective for CSA and CSB genes and their normal counterparts, grown for 24 h under various oxygen tensions (hyperoxic 21%, physioxic 5% and hypoxic 1%) to examine the fatty acid-based membrane remodeling by GC analysis of fatty acid methyl esters derived from membrane phospholipids. Overall, we first distinguished differences due to oxygen tensions: (a) hyperoxia induced a general boost of desaturase enzymatic activity in both normal and defective CSA and CSB cell lines, increasing monounsaturated fatty acids (MUFA), whereas polyunsaturated fatty acids (PUFA) did not undergo oxidative consumption; (b) hypoxia slowed down desaturase activities, mostly in CSA cell lines and defective CSB, causing saturated fatty acids (SFA) to increase, whereas PUFA levels diminished, suggesting their involvement in hypoxia-related signaling. CSB-deprived cells are the most sensitive to oxidation and CSA-deprived cells are the most sensitive to the radical-based formation of trans fatty acids (TFA). The results point to the need to finely differentiate biological targets connected to genetic impairments and, consequently, suggest the better definition of cell protection and treatments through accurate molecular profiling that includes membrane lipidomes.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Oxygen is important for lipid metabolism, being involved in both enzymatic transformations and oxidative reactivity, and is particularly influent when genetic diseases impair the repair machinery of the cells, such as described for Cockayne syndrome (CS). We used two cellular models of transformed fibroblasts defective for CSA and CSB genes and their normal counterparts, grown for 24 h under various oxygen tensions (hyperoxic 21%, physioxic 5% and hypoxic 1%) to examine the fatty acid-based membrane remodeling by GC analysis of fatty acid methyl esters derived from membrane phospholipids. Overall, we first distinguished differences due to oxygen tensions: (a) hyperoxia induced a general boost of desaturase enzymatic activity in both normal and defective CSA and CSB cell lines, increasing monounsaturated fatty acids (MUFA), whereas polyunsaturated fatty acids (PUFA) did not undergo oxidative consumption; (b) hypoxia slowed down desaturase activities, mostly in CSA cell lines and defective CSB, causing saturated fatty acids (SFA) to increase, whereas PUFA levels diminished, suggesting their involvement in hypoxia-related signaling. CSB-deprived cells are the most sensitive to oxidation and CSA-deprived cells are the most sensitive to the radical-based formation of trans fatty acids (TFA). The results point to the need to finely differentiate biological targets connected to genetic impairments and, consequently, suggest the better definition of cell protection and treatments through accurate molecular profiling that includes membrane lipidomes.
Bartolucci, Cecilia; Scognamiglio, Viviana; Antonacci, Amina; Fraceto, Leonardo Fernandes
What makes nanotechnologies applied to agriculture green? Journal Article
In: Nano Today, vol. 43, pp. 101389, 2022, ISSN: 1748-0132.
@article{BARTOLUCCI2022101389,
title = {What makes nanotechnologies applied to agriculture green?},
author = {Cecilia Bartolucci and Viviana Scognamiglio and Amina Antonacci and Leonardo Fernandes Fraceto},
url = {https://www.sciencedirect.com/science/article/pii/S1748013222000160},
doi = {10.1016/j.nantod.2022.101389},
issn = {1748-0132},
year = {2022},
date = {2022-04-01},
urldate = {2022-01-01},
journal = {Nano Today},
volume = {43},
pages = {101389},
abstract = {We describe a circular framework, divided into segments addressing specific aspects of potentially green interventions, that allows for a quick assessment of what makes nanotechnologies applied to agriculture green.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
We describe a circular framework, divided into segments addressing specific aspects of potentially green interventions, that allows for a quick assessment of what makes nanotechnologies applied to agriculture green.
Magrì, Antonio; Tabbì, Giovanni; Naletova, Irina; Attanasio, Francesco; Arena, Giuseppe; Rizzarelli, Enrico
In: International Journal of Molecular Sciences, vol. 23, no. 6, 2022, ISSN: 1422-0067.
@article{ijms23062929,
title = {A Deeper Insight in Metal Binding to the hCtr1 N-terminus Fragment: Affinity, Speciation and Binding Mode of Binuclear Cu2+ and Mononuclear Ag+ Complex Species},
author = {Antonio Magr\`{i} and Giovanni Tabb\`{i} and Irina Naletova and Francesco Attanasio and Giuseppe Arena and Enrico Rizzarelli},
url = {https://www.mdpi.com/1422-0067/23/6/2929},
doi = {10.3390/ijms23062929},
issn = {1422-0067},
year = {2022},
date = {2022-03-08},
urldate = {2022-01-01},
journal = {International Journal of Molecular Sciences},
volume = {23},
number = {6},
abstract = {Ctr1 regulates copper uptake and its intracellular distribution. The first 14 amino acid sequence of the Ctr1 ectodomain Ctr1(1-14) encompasses the characteristic Amino Terminal Cu2+ and Ni2+ binding motif (ATCUN) as well as the bis-His binding motif (His5 and His6). We report a combined thermodynamic and spectroscopic (UV-vis, CD, EPR) study dealing with the formation of Cu2+ homobinuclear complexes with Ctr1(1-14), the percentage of which is not negligible even in the presence of a small Cu2+ excess and clearly prevails at a M/L ratio of 1.9. Ascorbate fails to reduce Cu2+ when bound to the ATCUN motif, while it reduces Cu2+ when bound to the His5-His6 motif involved in the formation of binuclear species. The histidine diade characterizes the second binding site and is thought to be responsible for ascorbate oxidation. Binding constants and speciation of Ag+ complexes with Ctr1(1-14), which are assumed to mimic Cu+ interaction with N-terminus of Ctr1(1-14), were also determined. A preliminary immunoblot assay evidences that the anti-Ctr1 extracellular antibody recognizes Ctr1(1-14) in a different way from the longer Ctr1(1-25) that encompasses a second His and Met rich domain.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Ctr1 regulates copper uptake and its intracellular distribution. The first 14 amino acid sequence of the Ctr1 ectodomain Ctr1(1-14) encompasses the characteristic Amino Terminal Cu2+ and Ni2+ binding motif (ATCUN) as well as the bis-His binding motif (His5 and His6). We report a combined thermodynamic and spectroscopic (UV-vis, CD, EPR) study dealing with the formation of Cu2+ homobinuclear complexes with Ctr1(1-14), the percentage of which is not negligible even in the presence of a small Cu2+ excess and clearly prevails at a M/L ratio of 1.9. Ascorbate fails to reduce Cu2+ when bound to the ATCUN motif, while it reduces Cu2+ when bound to the His5-His6 motif involved in the formation of binuclear species. The histidine diade characterizes the second binding site and is thought to be responsible for ascorbate oxidation. Binding constants and speciation of Ag+ complexes with Ctr1(1-14), which are assumed to mimic Cu+ interaction with N-terminus of Ctr1(1-14), were also determined. A preliminary immunoblot assay evidences that the anti-Ctr1 extracellular antibody recognizes Ctr1(1-14) in a different way from the longer Ctr1(1-25) that encompasses a second His and Met rich domain.
Falco, Mariarosaria De; Felice, Mariarita De; Rota, Federica; Zappi, Daniele; Antonacci, Amina; Scognamiglio, Viviana
Next-generation diagnostics: Augmented sensitivity in amplification-powered biosensing Journal Article
In: TrAC Trends in Analytical Chemistry, vol. 148, pp. 116538, 2022, ISSN: 0165-9936.
@article{DEFALCO2022116538,
title = {Next-generation diagnostics: Augmented sensitivity in amplification-powered biosensing},
author = {Mariarosaria De Falco and Mariarita De Felice and Federica Rota and Daniele Zappi and Amina Antonacci and Viviana Scognamiglio},
url = {https://www.sciencedirect.com/science/article/pii/S0165993622000218},
doi = {10.1016/j.trac.2022.116538},
issn = {0165-9936},
year = {2022},
date = {2022-03-01},
urldate = {2022-01-01},
journal = {TrAC Trends in Analytical Chemistry},
volume = {148},
pages = {116538},
abstract = {Among the ultimate requirements of biosensor technology, sensitivity, stability, and specificity are undoubtedly crucial features to enter the market. Actually, sensitivity is a major drawback for biosensors, especially where there is a low abundance of targets. To address this concern, biosensor technology has been supported by effective methodologies for the target isothermal amplification, successfully applied to sensitively detect nucleic acids of viral and bacterial sources, capable to operate in low-resource settings and instrumentations, an important prerequisite for microfluidics and point-of-care diagnostics. This review of 133 refs provides an in-depth description of the available methods for isothermal amplification of nucleic acids, with pros and cons, and their integration into different detection systems. The potential of combining the amplification-powered biosensor with technological advances in the branches of nanotechnology and paper microfluidics is also proved by excellent examples from the literature.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Among the ultimate requirements of biosensor technology, sensitivity, stability, and specificity are undoubtedly crucial features to enter the market. Actually, sensitivity is a major drawback for biosensors, especially where there is a low abundance of targets. To address this concern, biosensor technology has been supported by effective methodologies for the target isothermal amplification, successfully applied to sensitively detect nucleic acids of viral and bacterial sources, capable to operate in low-resource settings and instrumentations, an important prerequisite for microfluidics and point-of-care diagnostics. This review of 133 refs provides an in-depth description of the available methods for isothermal amplification of nucleic acids, with pros and cons, and their integration into different detection systems. The potential of combining the amplification-powered biosensor with technological advances in the branches of nanotechnology and paper microfluidics is also proved by excellent examples from the literature.
Sciacca, Michele F. M.; Naletova, Irina; Giuffrida, Maria Laura; Attanasio, Francesco
Semax, a Synthetic Regulatory Peptide, Affects Copper-Induced Abeta Aggregation and Amyloid Formation in Artificial Membrane Models Journal Article
In: ACS Chemical Neuroscience, vol. 13, no. 4, pp. 486-496, 2022, (PMID: 35080861).
@article{doi:10.1021/acschemneuro.1c00707,
title = {Semax, a Synthetic Regulatory Peptide, Affects Copper-Induced Abeta Aggregation and Amyloid Formation in Artificial Membrane Models},
author = {Michele F. M. Sciacca and Irina Naletova and Maria Laura Giuffrida and Francesco Attanasio},
url = {https://doi.org/10.1021/acschemneuro.1c00707},
doi = {10.1021/acschemneuro.1c00707},
year = {2022},
date = {2022-02-16},
urldate = {2022-02-16},
journal = {ACS Chemical Neuroscience},
volume = {13},
number = {4},
pages = {486-496},
abstract = {Alzheimer’s disease, the most common form of dementia, is characterized by the aggregation of amyloid beta protein (Aβ). The aggregation and toxicity of Aβ are strongly modulated by metal ions and phospholipidic membranes. In particular, Cu2+ ions play a pivotal role in modulating Aβ aggregation. Although in the last decades several natural or synthetic compounds were evaluated as candidate drugs, to date, no treatments are available for the pathology. Multifunctional compounds able to both inhibit fibrillogenesis, and in particular the formation of oligomeric species, and prevent the formation of the Aβ:Cu2+ complex are of particular interest. Here we tested the anti-aggregating properties of a heptapeptide, Semax, an ACTH-like peptide, which is known to form a stable complex with Cu2+ ions and has been proven to have neuroprotective and nootropic effects. We demonstrated through a combination of spectrofluorometric, calorimetric, and MTT assays that Semax not only is able to prevent the formation of Aβ:Cu2+ complexes but also has anti-aggregating and protective properties especially in the presence of Cu2+. The results suggest that Semax inhibits fiber formation by interfering with the fibrillogenesis of Aβ:Cu2+ complexes.},
note = {PMID: 35080861},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Alzheimer’s disease, the most common form of dementia, is characterized by the aggregation of amyloid beta protein (Aβ). The aggregation and toxicity of Aβ are strongly modulated by metal ions and phospholipidic membranes. In particular, Cu2+ ions play a pivotal role in modulating Aβ aggregation. Although in the last decades several natural or synthetic compounds were evaluated as candidate drugs, to date, no treatments are available for the pathology. Multifunctional compounds able to both inhibit fibrillogenesis, and in particular the formation of oligomeric species, and prevent the formation of the Aβ:Cu2+ complex are of particular interest. Here we tested the anti-aggregating properties of a heptapeptide, Semax, an ACTH-like peptide, which is known to form a stable complex with Cu2+ ions and has been proven to have neuroprotective and nootropic effects. We demonstrated through a combination of spectrofluorometric, calorimetric, and MTT assays that Semax not only is able to prevent the formation of Aβ:Cu2+ complexes but also has anti-aggregating and protective properties especially in the presence of Cu2+. The results suggest that Semax inhibits fiber formation by interfering with the fibrillogenesis of Aβ:Cu2+ complexes.
Sasso, Gregorio Dal; Dalconi, Maria Chiara; Ferrari, Giorgio; Pedersen, Jan Skov; Tamburini, Sergio; Bertolotti, Federica; Guagliardi, Antonietta; Bruno, Marco; Valentini, Luca; Artioli, Gilberto
An Atomistic Model Describing the Structure and Morphology of Cu-Doped C-S-H Hardening Accelerator Nanoparticles Journal Article
In: Nanomaterials (Basel), vol. 12, no. 3, 2022, ISSN: 2079-4991.
@article{pmid35159685,
title = {An Atomistic Model Describing the Structure and Morphology of Cu-Doped C-S-H Hardening Accelerator Nanoparticles},
author = {Gregorio Dal Sasso and Maria Chiara Dalconi and Giorgio Ferrari and Jan Skov Pedersen and Sergio Tamburini and Federica Bertolotti and Antonietta Guagliardi and Marco Bruno and Luca Valentini and Gilberto Artioli},
doi = {10.3390/nano12030342},
issn = {2079-4991},
year = {2022},
date = {2022-01-21},
urldate = {2022-01-01},
journal = {Nanomaterials (Basel)},
volume = {12},
number = {3},
abstract = {Calcium silicate hydrate (C-S-H) is the main binding phase in Portland cement. The addition of C-S-H nanoparticles as nucleation seeds has successfully been used to accelerate the hydration process and the precipitation of binding phases either in conventional Portland cement or in alternative binders. Indeed, the modulation of the hydration kinetics during the early-stage dissolution-precipitation reactions, by acting on the nucleation and growth of binding phases, improves the early strength development. The fine-tuning of concrete properties in terms of compressive strength and durability by designed structural modifications can be achieved through the detailed description of the reaction products at the atomic scale. The nano-sized, chemically complex and structurally disordered nature of these phases hamper their thorough structural characterization. To this aim, we implement a novel multi-scale approach by combining forefront small-angle X-ray scattering (SAXS) and synchrotron wide-angle X-ray total scattering (WAXTS) analyses for the characterization of Cu-doped C-S-H nanoparticles dispersed in a colloidal suspension, used as hardening accelerator. SAXS and WAXTS data were analyzed under a unified modeling approach by developing suitable atomistic models for C-S-H nanoparticles to be used to simulate the experimental X-ray scattering pattern through the Debye scattering equation. The optimization of atomistic models against the experimental pattern, together with complementary information on the structural local order from Si solid-state nuclear magnetic resonance and X-ray absorption spectroscopy, provided a comprehensive description of the structure, size and morphology of C-S-H nanoparticles from the atomic to the nanometer scale. C-S-H nanoparticles were modeled as an assembly of layers composed of 7-fold coordinated Ca atoms and decorated by silicate dimers and chains. The structural layers are a few tens of nanometers in length and width, with a crystal structure resembling that of a defective tobermorite, but lacking any ordering between stacking layers.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Calcium silicate hydrate (C-S-H) is the main binding phase in Portland cement. The addition of C-S-H nanoparticles as nucleation seeds has successfully been used to accelerate the hydration process and the precipitation of binding phases either in conventional Portland cement or in alternative binders. Indeed, the modulation of the hydration kinetics during the early-stage dissolution-precipitation reactions, by acting on the nucleation and growth of binding phases, improves the early strength development. The fine-tuning of concrete properties in terms of compressive strength and durability by designed structural modifications can be achieved through the detailed description of the reaction products at the atomic scale. The nano-sized, chemically complex and structurally disordered nature of these phases hamper their thorough structural characterization. To this aim, we implement a novel multi-scale approach by combining forefront small-angle X-ray scattering (SAXS) and synchrotron wide-angle X-ray total scattering (WAXTS) analyses for the characterization of Cu-doped C-S-H nanoparticles dispersed in a colloidal suspension, used as hardening accelerator. SAXS and WAXTS data were analyzed under a unified modeling approach by developing suitable atomistic models for C-S-H nanoparticles to be used to simulate the experimental X-ray scattering pattern through the Debye scattering equation. The optimization of atomistic models against the experimental pattern, together with complementary information on the structural local order from Si solid-state nuclear magnetic resonance and X-ray absorption spectroscopy, provided a comprehensive description of the structure, size and morphology of C-S-H nanoparticles from the atomic to the nanometer scale. C-S-H nanoparticles were modeled as an assembly of layers composed of 7-fold coordinated Ca atoms and decorated by silicate dimers and chains. The structural layers are a few tens of nanometers in length and width, with a crystal structure resembling that of a defective tobermorite, but lacking any ordering between stacking layers.
Consoli, Grazia Maria Letizia; Giuffrida, Maria Laura; Satriano, Cristina; Musumeci, Teresa; Forte, Giuseppe; Petralia, Salvatore
A novel facile one-pot synthesis of photothermally responsive carbon polymer dots as promising drug nanocarriers Journal Article
In: Chem. Commun., vol. 58, pp. 3126-3129, 2022.
@article{D1CC06530K,
title = {A novel facile one-pot synthesis of photothermally responsive carbon polymer dots as promising drug nanocarriers},
author = {Grazia Maria Letizia Consoli and Maria Laura Giuffrida and Cristina Satriano and Teresa Musumeci and Giuseppe Forte and Salvatore Petralia},
url = {http://dx.doi.org/10.1039/D1CC06530K},
doi = {10.1039/D1CC06530K},
year = {2022},
date = {2022-01-12},
urldate = {2022-01-12},
journal = {Chem. Commun.},
volume = {58},
pages = {3126-3129},
publisher = {The Royal Society of Chemistry},
abstract = {Luminescent and photothermic carbon polymer dots (CPDs\textendashPNM), composed of a carbonized core and cross-linked chains of poly(N-isopropylacrylamide), were synthetized by a novel, simple, solvent- and reagent-free method. The formation of CPDs\textendashPNM was controlled by both temperature and heating time. The CPDs\textendashPNM exhibited LCST behaviour, high photothermal conversion efficiency, curcumin loading capacity and no toxicity to eukaryotic cells. Proof of concept experiments confirmed an excellent thermally induced drug release activity to be used for photothermally controlled drug release.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Luminescent and photothermic carbon polymer dots (CPDs–PNM), composed of a carbonized core and cross-linked chains of poly(N-isopropylacrylamide), were synthetized by a novel, simple, solvent- and reagent-free method. The formation of CPDs–PNM was controlled by both temperature and heating time. The CPDs–PNM exhibited LCST behaviour, high photothermal conversion efficiency, curcumin loading capacity and no toxicity to eukaryotic cells. Proof of concept experiments confirmed an excellent thermally induced drug release activity to be used for photothermally controlled drug release.
Sandomenico, Annamaria; Gogliettino, Marta; Iaccarino, Emanuela; Fusco, Carmela; Caporale, Andrea; Ruvo, Menotti; Palmieri, Gianna; Cocca, Ennio
Oxidized Substrates of APEH as a Tool to Study the Endoprotease Activity of the Enzyme Journal Article
In: Int J Mol Sci, vol. 23, no. 1, 2022, ISSN: 1422-0067.
@article{pmid35008880,
title = {Oxidized Substrates of APEH as a Tool to Study the Endoprotease Activity of the Enzyme},
author = {Annamaria Sandomenico and Marta Gogliettino and Emanuela Iaccarino and Carmela Fusco and Andrea Caporale and Menotti Ruvo and Gianna Palmieri and Ennio Cocca},
doi = {10.3390/ijms23010443},
issn = {1422-0067},
year = {2022},
date = {2022-01-01},
urldate = {2021-12-01},
journal = {Int J Mol Sci},
volume = {23},
number = {1},
abstract = {APEH is a ubiquitous and cytosolic serine protease belonging to the prolyl oligopeptidase (POP) family, playing a critical role in the processes of degradation of proteins through both exo- and endopeptidase events. Endopeptidase activity has been associated with protein oxidation; however, the actual mechanisms have yet to be elucidated. We show that a synthetic fragment of GDF11 spanning the region 48-64 acquires sensitivity to the endopeptidase activity of APEH only when the methionines are transformed into the corresponding sulphoxide derivatives. The data suggest that the presence of sulphoxide-modified methionines is an important prerequisite for the substrates to be processed by APEH and that the residue is crucial for switching the enzyme activity from exo- to endoprotease. The cleavage occurs on residues placed on the C-terminal side of Met(O), with an efficiency depending on the methionine adjacent residues, which thereby may play a crucial role in driving and modulating APEH endoprotease activity.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
APEH is a ubiquitous and cytosolic serine protease belonging to the prolyl oligopeptidase (POP) family, playing a critical role in the processes of degradation of proteins through both exo- and endopeptidase events. Endopeptidase activity has been associated with protein oxidation; however, the actual mechanisms have yet to be elucidated. We show that a synthetic fragment of GDF11 spanning the region 48-64 acquires sensitivity to the endopeptidase activity of APEH only when the methionines are transformed into the corresponding sulphoxide derivatives. The data suggest that the presence of sulphoxide-modified methionines is an important prerequisite for the substrates to be processed by APEH and that the residue is crucial for switching the enzyme activity from exo- to endoprotease. The cleavage occurs on residues placed on the C-terminal side of Met(O), with an efficiency depending on the methionine adjacent residues, which thereby may play a crucial role in driving and modulating APEH endoprotease activity.
Bolognino, Isabella; Carrieri, Antonio; Purgatorio, Rosa; Catto, Marco; Caliandro, Rocco; Carrozzini, Benedetta; Belviso, Benny Danilo; Majellaro, Maria; Sotelo, Eddy; Cellamare, Saverio; Altomare, Cosimo Damiano
In: Separations, vol. 9, no. 1, 2022, ISSN: 2297-8739.
@article{separations9010007,
title = {Enantiomeric Separation and Molecular Modelling of Bioactive 4-Aryl-3,4-dihydropyrimidin-2(1H)-one Ester Derivatives on Teicoplanin-Based Chiral Stationary Phase},
author = {Isabella Bolognino and Antonio Carrieri and Rosa Purgatorio and Marco Catto and Rocco Caliandro and Benedetta Carrozzini and Benny Danilo Belviso and Maria Majellaro and Eddy Sotelo and Saverio Cellamare and Cosimo Damiano Altomare},
url = {https://www.mdpi.com/2297-8739/9/1/7},
doi = {10.3390/separations9010007},
issn = {2297-8739},
year = {2022},
date = {2022-01-01},
urldate = {2022-01-01},
journal = {Separations},
volume = {9},
number = {1},
abstract = {The enantiomeric separation of 15 racemic 4-aryl-3,4-dihydropyrimidin-2(1H)-one (DHP) alkoxycarbonyl esters, some of which proved to be highly active as A2B adenosine receptor antagonists, was carried out by HPLC on ChirobioticTM TAG, a chiral stationary phase (CSP) bearing teicoplanin aglycone (TAG) as the chiral selector. The racemic compounds were separated under polar organic (PO) conditions. Preliminarily, the same selectands were investigated on three different Pirkle-type CSPs in normal-phase (NP) conditions. A baseline separation was successfully obtained on TAG-based CSPs for the majority of compounds, some of which achieved high enantioselectivity ratios (\α > 2) in contrast with the smaller \α values (1-1.5) and the lack of baseline resolution observed with the Pirkle-type CSPs. In particular, the racemic tetrazole-fused DHP ester derivatives, namely compounds 8 and 9, were separated on TAG-based HPLC columns with noteworthy \α values (8.8 and 6.0, respectively), demonstrating the potential of the method for preparative purposes. A competition experiment, carried out with a racemic analyte (6) by adding N-acetyl-d-alanine (NADA) to the mobile phase, suggested that H-bonding interactions involved in the recognition of the natural dipeptide ligand d-Ala-d-Ala into the TAG cleft should be critical for enantioselective recognition of 4-aryl DHPs by TAG. The X-ray crystal structure of TAG was elucidated at a 0.77 \Å resolution, whereas the calculation of molecular descriptors of size, polar, and H-bond interactions, were complemented with molecular docking and molecular dynamics calculations, shedding light on repulsive (steric effects) and attractive (H-bond\—polar and apolar) interactions between 4-aryl DHP selectands and TAG chiral selectors.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The enantiomeric separation of 15 racemic 4-aryl-3,4-dihydropyrimidin-2(1H)-one (DHP) alkoxycarbonyl esters, some of which proved to be highly active as A2B adenosine receptor antagonists, was carried out by HPLC on ChirobioticTM TAG, a chiral stationary phase (CSP) bearing teicoplanin aglycone (TAG) as the chiral selector. The racemic compounds were separated under polar organic (PO) conditions. Preliminarily, the same selectands were investigated on three different Pirkle-type CSPs in normal-phase (NP) conditions. A baseline separation was successfully obtained on TAG-based CSPs for the majority of compounds, some of which achieved high enantioselectivity ratios (α > 2) in contrast with the smaller α values (1–1.5) and the lack of baseline resolution observed with the Pirkle-type CSPs. In particular, the racemic tetrazole-fused DHP ester derivatives, namely compounds 8 and 9, were separated on TAG-based HPLC columns with noteworthy α values (8.8 and 6.0, respectively), demonstrating the potential of the method for preparative purposes. A competition experiment, carried out with a racemic analyte (6) by adding N-acetyl-d-alanine (NADA) to the mobile phase, suggested that H-bonding interactions involved in the recognition of the natural dipeptide ligand d-Ala-d-Ala into the TAG cleft should be critical for enantioselective recognition of 4-aryl DHPs by TAG. The X-ray crystal structure of TAG was elucidated at a 0.77 Å resolution, whereas the calculation of molecular descriptors of size, polar, and H-bond interactions, were complemented with molecular docking and molecular dynamics calculations, shedding light on repulsive (steric effects) and attractive (H-bond—polar and apolar) interactions between 4-aryl DHP selectands and TAG chiral selectors.
2021
Righini, Guido; Simonetti, Marco
PCTO: Competenze Digitali per i nuovi cittadini della scienza Journal Article
In: SMART eLAB, vol. 17, pp. 13–21, 2021.
@article{Righini_Simonetti_2021,
title = {PCTO: Competenze Digitali per i nuovi cittadini della scienza},
author = {Guido Righini and Marco Simonetti},
url = {https://calliope.cnr.it/index.php/smartelab/article/view/190},
doi = {10.30441/smartelab.v17i.190},
year = {2021},
date = {2021-12-30},
urldate = {2021-12-01},
journal = {SMART eLAB},
volume = {17},
pages = {13\textendash21},
abstract = {La diffusione delle tecnologie digitali di internet e della comunicazione (TIC) coinvolge molti aspetti della nostra vita. Attraverso l’uso delle TIC abbiamo l’opportunit\`{a} di accedere facilmente alle informazioni e alle conoscenze necessarie per il nostro lavoro, il tempo libero, la formazione, la cura della persona ecc. Le nuove generazioni si stanno formando in un mondo in cui le TIC sono sempre pi\`{u} presenti; \`{e} proprio grazie ad esse se non hanno interrotto il loro percorso formativo durante l’emergenza sanitaria da Covid-19. Per un uso efficace e consapevole delle tecnologie digitali \`{e} necessario acquisire delle specifiche competenze trasversali da aggiungere a quelle specifiche dei diversi ambiti lavorativi e professionali. Queste competenze possono essere sviluppate nei giovani attraverso percorsi formativi ad hoc. In questo articolo sar\`{a} discusso la progettazione e la realizzazione di un percorso formativo sulle competenze digitali.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
La diffusione delle tecnologie digitali di internet e della comunicazione (TIC) coinvolge molti aspetti della nostra vita. Attraverso l’uso delle TIC abbiamo l’opportunità di accedere facilmente alle informazioni e alle conoscenze necessarie per il nostro lavoro, il tempo libero, la formazione, la cura della persona ecc. Le nuove generazioni si stanno formando in un mondo in cui le TIC sono sempre più presenti; è proprio grazie ad esse se non hanno interrotto il loro percorso formativo durante l’emergenza sanitaria da Covid-19. Per un uso efficace e consapevole delle tecnologie digitali è necessario acquisire delle specifiche competenze trasversali da aggiungere a quelle specifiche dei diversi ambiti lavorativi e professionali. Queste competenze possono essere sviluppate nei giovani attraverso percorsi formativi ad hoc. In questo articolo sarà discusso la progettazione e la realizzazione di un percorso formativo sulle competenze digitali.
Baldi, Marina; Simonetti, Marco; Righini, Guido
Agricultural Meteorology for a Climate Smart Agriculture. Course Report Journal Article
In: SMART eLAB, vol. 17, pp. 1–12, 2021.
@article{Baldi_Simonetti_Righini_2021,
title = {Agricultural Meteorology for a Climate Smart Agriculture. Course Report},
author = {Marina Baldi and Marco Simonetti and Guido Righini},
url = {https://calliope.cnr.it/index.php/smartelab/article/view/188},
doi = {10.30441/smartelab.v17i.188},
year = {2021},
date = {2021-12-30},
urldate = {2021-12-01},
journal = {SMART eLAB},
volume = {17},
pages = {1\textendash12},
abstract = {The WMO-RTC (World Meteorological Organization \textendash Regional Training Centre) run in Italy by the Institute of BioEconomy of the National research Council is part of a Network of Centres whose main aim is to promote education and training in meteorology, hydrology, climate and related areas. The Italian Centre, since it was established in Florence, is offering training in agrometeorology, agroclimatology, climate impacts, disaster risk reduction and climate services and communication, with short-term courses and workshops, long-term stages, rowing seminars, training events on demand. Training solutions adopted include Face-to-Face events, Distance Learning, and E-Learning packages for self-paced learning. In 2020 the Italian Association of Agrometeorology (AIAM) launched the 1st Edition of the International Advanced School in Agricultural Meteorology, and the WMO-RTC, in agreement with AIAM and the important contribution of FAO, designed and put in place a new course on Climate Smart Agriculture to be held face-to-face at CNR headquarters in Rome. Due to the Covid-19 pandemic, the format of the school was completely revised, the course opened to a much wider audience (43 students from 19 Countries) and run (synchronous) fully online. The success of the school was determined by several factors including: the theme of the school, the expertise of appointed trainers, and the use of an easy to use e-learning platform like Moodle. In addition, the continuous support ensured by the technical staff, the role played by facilitators and chairs of the sessions, and the cohesion of the scientific committee and technical staff were all ingredients contributing to the success of this online learning initiative In this paper, Authors discuss the results of the training initiative, and present the comments from participants to the school.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The WMO-RTC (World Meteorological Organization – Regional Training Centre) run in Italy by the Institute of BioEconomy of the National research Council is part of a Network of Centres whose main aim is to promote education and training in meteorology, hydrology, climate and related areas. The Italian Centre, since it was established in Florence, is offering training in agrometeorology, agroclimatology, climate impacts, disaster risk reduction and climate services and communication, with short-term courses and workshops, long-term stages, rowing seminars, training events on demand. Training solutions adopted include Face-to-Face events, Distance Learning, and E-Learning packages for self-paced learning. In 2020 the Italian Association of Agrometeorology (AIAM) launched the 1st Edition of the International Advanced School in Agricultural Meteorology, and the WMO-RTC, in agreement with AIAM and the important contribution of FAO, designed and put in place a new course on Climate Smart Agriculture to be held face-to-face at CNR headquarters in Rome. Due to the Covid-19 pandemic, the format of the school was completely revised, the course opened to a much wider audience (43 students from 19 Countries) and run (synchronous) fully online. The success of the school was determined by several factors including: the theme of the school, the expertise of appointed trainers, and the use of an easy to use e-learning platform like Moodle. In addition, the continuous support ensured by the technical staff, the role played by facilitators and chairs of the sessions, and the cohesion of the scientific committee and technical staff were all ingredients contributing to the success of this online learning initiative In this paper, Authors discuss the results of the training initiative, and present the comments from participants to the school.
Paoletti, Francesca; Lamba, Doriano
Small Endogenous Ligands Modulation of Nerve Growth Factor Bioactivity: A Structural Biology Overview Journal Article
In: Cells, vol. 10, no. 12, 2021, ISSN: 2073-4409.
@article{pmid34943971,
title = {Small Endogenous Ligands Modulation of Nerve Growth Factor Bioactivity: A Structural Biology Overview},
author = {Francesca Paoletti and Doriano Lamba},
doi = {10.3390/cells10123462},
issn = {2073-4409},
year = {2021},
date = {2021-12-08},
urldate = {2021-01-01},
journal = {Cells},
volume = {10},
number = {12},
abstract = {Experiments with cell cultures and animal models have provided solid support for the assumption that Nerve Growth Factor (NGF) plays a key role in the regulation of neuronal cell survival and death. Recently, endogenous ligands have been proposed as physiological modulators of NGF biological activity as part of this regulatory cascade. However, the structural and mechanistic determinants for NGF bioactivity remain to be elucidated. We recently unveiled, by an integrated structural biology approach, the ATP binding sites of NGF and investigated the effects on TrkA and p75 receptors binding. These results pinpoint ATP as a genuine endogenous modulator of NGF signaling, paving the way to the characterization of not-yet-identified chemical diverse endogenous biological active small molecules as novel modulators of NGF. The present review aims at providing an overview of the currently available 3D structures of NGF in complex with different small endogenous ligands, featuring the molecular footprints of the small molecules binding. This knowledge is essential for further understanding the functional role of small endogenous ligands in the modulation of neurotrophins signaling in physiological and pathological conditions and for better exploiting the therapeutic potentialities of NGF.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Experiments with cell cultures and animal models have provided solid support for the assumption that Nerve Growth Factor (NGF) plays a key role in the regulation of neuronal cell survival and death. Recently, endogenous ligands have been proposed as physiological modulators of NGF biological activity as part of this regulatory cascade. However, the structural and mechanistic determinants for NGF bioactivity remain to be elucidated. We recently unveiled, by an integrated structural biology approach, the ATP binding sites of NGF and investigated the effects on TrkA and p75 receptors binding. These results pinpoint ATP as a genuine endogenous modulator of NGF signaling, paving the way to the characterization of not-yet-identified chemical diverse endogenous biological active small molecules as novel modulators of NGF. The present review aims at providing an overview of the currently available 3D structures of NGF in complex with different small endogenous ligands, featuring the molecular footprints of the small molecules binding. This knowledge is essential for further understanding the functional role of small endogenous ligands in the modulation of neurotrophins signaling in physiological and pathological conditions and for better exploiting the therapeutic potentialities of NGF.
Boi, Dalila; Souvalidou, Fani; Capelli, Davide; Polverino, Federica; Marini, Grazia; Montanari, Roberta; Pochetti, Giorgio; Tramonti, Angela; Contestabile, Roberto; Trisciuoglio, Daniela; Carpinelli, Patrizia; Ascanelli, Camilla; Lindon, Catherine; Leo, Alessandro De; Saviano, Michele; Santo, Roberto Di; Costi, Roberta; Guarguaglini, Giulia; Paiardini, Alessandro
PHA-680626 Is an Effective Inhibitor of the Interaction between Aurora-A and N-Myc Journal Article
In: International Journal of Molecular Sciences, vol. 22, no. 23, 2021, ISSN: 1422-0067.
@article{ijms222313122,
title = {PHA-680626 Is an Effective Inhibitor of the Interaction between Aurora-A and N-Myc},
author = {Dalila Boi and Fani Souvalidou and Davide Capelli and Federica Polverino and Grazia Marini and Roberta Montanari and Giorgio Pochetti and Angela Tramonti and Roberto Contestabile and Daniela Trisciuoglio and Patrizia Carpinelli and Camilla Ascanelli and Catherine Lindon and Alessandro De Leo and Michele Saviano and Roberto Di Santo and Roberta Costi and Giulia Guarguaglini and Alessandro Paiardini},
url = {https://www.mdpi.com/1422-0067/22/23/13122},
doi = {10.3390/ijms222313122},
issn = {1422-0067},
year = {2021},
date = {2021-12-04},
urldate = {2021-01-01},
journal = {International Journal of Molecular Sciences},
volume = {22},
number = {23},
abstract = {Neuroblastoma is a severe childhood disease, accounting for ~10% of all infant cancers. The amplification of the MYCN gene, coding for the N-Myc transcription factor, is an essential marker correlated with tumor progression and poor prognosis. In neuroblastoma cells, the mitotic kinase Aurora-A (AURKA), also frequently overexpressed in cancer, prevents N-Myc degradation by directly binding to a highly conserved N-Myc region. As a result, elevated levels of N-Myc are observed. During recent years, it has been demonstrated that some ATP competitive inhibitors of AURKA also cause essential conformational changes in the structure of the activation loop of the kinase that prevents N-Myc binding, thus impairing the formation of the AURKA/N-Myc complex. In this study, starting from a screening of crystal structures of AURKA in complexes with known inhibitors, we identified additional compounds affecting the conformation of the kinase activation loop. We assessed the ability of such compounds to disrupt the interaction between AURKA and N-Myc in vitro, using Surface Plasmon Resonance competition assays, and in tumor cell lines overexpressing MYCN, by performing Proximity Ligation Assays. Finally, their effects on N-Myc cellular levels and cell viability were investigated. Our results identify PHA-680626 as an amphosteric inhibitor both in vitro and in MYCN overexpressing cell lines, thus expanding the repertoire of known conformational disrupting inhibitors of the AURKA/N-Myc complex and confirming that altering the conformation of the activation loop of AURKA with a small molecule is an effective strategy to destabilize the AURKA/N-Myc interaction in neuroblastoma cancer cells.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Neuroblastoma is a severe childhood disease, accounting for ~10% of all infant cancers. The amplification of the MYCN gene, coding for the N-Myc transcription factor, is an essential marker correlated with tumor progression and poor prognosis. In neuroblastoma cells, the mitotic kinase Aurora-A (AURKA), also frequently overexpressed in cancer, prevents N-Myc degradation by directly binding to a highly conserved N-Myc region. As a result, elevated levels of N-Myc are observed. During recent years, it has been demonstrated that some ATP competitive inhibitors of AURKA also cause essential conformational changes in the structure of the activation loop of the kinase that prevents N-Myc binding, thus impairing the formation of the AURKA/N-Myc complex. In this study, starting from a screening of crystal structures of AURKA in complexes with known inhibitors, we identified additional compounds affecting the conformation of the kinase activation loop. We assessed the ability of such compounds to disrupt the interaction between AURKA and N-Myc in vitro, using Surface Plasmon Resonance competition assays, and in tumor cell lines overexpressing MYCN, by performing Proximity Ligation Assays. Finally, their effects on N-Myc cellular levels and cell viability were investigated. Our results identify PHA-680626 as an amphosteric inhibitor both in vitro and in MYCN overexpressing cell lines, thus expanding the repertoire of known conformational disrupting inhibitors of the AURKA/N-Myc complex and confirming that altering the conformation of the activation loop of AURKA with a small molecule is an effective strategy to destabilize the AURKA/N-Myc interaction in neuroblastoma cancer cells.
Campos-Escamilla, Camila; Siliqi, Dritan; Gonzalez-Ramirez, Luis A; Lopez-Sanchez, Carmen; Gavira, Jose Antonio; Moreno, Abel
X-ray Characterization of Conformational Changes of Human Apo- and Holo-Transferrin Journal Article
In: Int J Mol Sci, vol. 22, no. 24, 2021, ISSN: 1422-0067.
@article{pmid34948188,
title = {X-ray Characterization of Conformational Changes of Human Apo- and Holo-Transferrin},
author = {Camila Campos-Escamilla and Dritan Siliqi and Luis A Gonzalez-Ramirez and Carmen Lopez-Sanchez and Jose Antonio Gavira and Abel Moreno},
doi = {10.3390/ijms222413392},
issn = {1422-0067},
year = {2021},
date = {2021-12-01},
urldate = {2021-12-01},
journal = {Int J Mol Sci},
volume = {22},
number = {24},
abstract = {Human serum transferrin (Tf) is a bilobed glycoprotein whose function is to transport iron through receptor-mediated endocytosis. The mechanism for iron release is pH-dependent and involves conformational changes in the protein, thus making it an attractive system for possible biomedical applications. In this contribution, two powerful X-ray techniques, namely Macromolecular X-ray Crystallography (MX) and Small Angle X-ray Scattering (SAXS), were used to study the conformational changes of iron-free (apo) and iron-loaded (holo) transferrin in crystal and solution states, respectively, at three different pH values of physiological relevance. A crystallographic model of glycosylated apo-Tf was obtained at 3.0 r{A} resolution, which did not resolve further despite many efforts to improve crystal quality. In the solution, apo-Tf remained mostly globular in all the pH conditions tested; however, the co-existence of closed, partially open, and open conformations was observed for holo-Tf, which showed a more elongated and flexible shape overall.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Human serum transferrin (Tf) is a bilobed glycoprotein whose function is to transport iron through receptor-mediated endocytosis. The mechanism for iron release is pH-dependent and involves conformational changes in the protein, thus making it an attractive system for possible biomedical applications. In this contribution, two powerful X-ray techniques, namely Macromolecular X-ray Crystallography (MX) and Small Angle X-ray Scattering (SAXS), were used to study the conformational changes of iron-free (apo) and iron-loaded (holo) transferrin in crystal and solution states, respectively, at three different pH values of physiological relevance. A crystallographic model of glycosylated apo-Tf was obtained at 3.0 Å resolution, which did not resolve further despite many efforts to improve crystal quality. In the solution, apo-Tf remained mostly globular in all the pH conditions tested; however, the co-existence of closed, partially open, and open conformations was observed for holo-Tf, which showed a more elongated and flexible shape overall.