Alessandro Contini - Academia.edu (original) (raw)
Papers by Alessandro Contini
Synlett, 2012
Abstract A series of pentyl-sulfonyl amidines was obtained using a multicomponent synthesis proce... more Abstract A series of pentyl-sulfonyl amidines was obtained using a multicomponent synthesis process. The rearrangement of unstable tosylazide-cyclopentanonenamine cycloadducts yielded a diazoalkane intermediate. This primary, unstable reaction product showed good reactivity with certain acid compounds in order to form the corresponding derivatives.
Biochimica Et Biophysica Acta Proteins and Proteomics, Sep 11, 2014
The Maf protein family belongs to the activator protein 1 (AP-1) superfamily of transcription fac... more The Maf protein family belongs to the activator protein 1 (AP-1) superfamily of transcription factors that bind specific DNA target sequences through a basic region and exploit a leucine zipper (LZ) motif for protein-protein interactions leading to homo- or hetero-dimerization. Mafs unique DNA-binding domain contains a highly conserved extended homology region (EHR) that allows to recognize longer DNA sequences than other basic leucine zipper (bZIP) transcription factors. Inspired by the fact that overexpression of Mafs is observed in about 50% of cases of multiple myeloma, a hematological malignant disorder, we undertook a peptide inhibitor approach. The LZ domain of c-Maf, one of large Mafs, was produced by solid phase peptide synthesis. We characterized its secondary structure and dimerization properties, and found that dimerization and folding events are strictly coupled. Moreover, potential peptidic c-Maf dimerization inhibitors were computationally designed and synthesized. These compounds were demonstrated by circular dichroism (CD) spectroscopy and MALDI-TOF mass spectrometry to bind to c-Maf LZ monomers, to drive folding of their partially disordered structure and to efficiently compete with dimerization, suggesting a way for interfering with the function of c-Maf and, more generally, of intrinsically disordered proteins, till now considered undruggable targets.
Cheminform, Feb 22, 2011
AbstractA highly diastereoselective and very efficient method to prepare title compounds is repor... more AbstractA highly diastereoselective and very efficient method to prepare title compounds is reported.
Journal of Protein Chemistry, Nov 18, 2008
Activity assays, conformational changes and transitional switches between secondary structures of... more Activity assays, conformational changes and transitional switches between secondary structures of a peroxidase from Euphorbia characias were studied in the presence of trifluoroethanol and in the presence or absence of calcium ions. The addition of trifluoroethanol up to 10-20% first induced a drastic decrease of a-helix content followed by an increase of tryptophan fluorescence emission intensity, a progressive re-induction of the formation of a-helical elements concomitant with loss of enzyme activity. In the presence of calcium ions, the fluorescence of the enzyme almost remained unchanged in the trifluoroethanol concentration range 5-20%. Further increase in trifluoroethanol concentration led to a protein structure characterized by a progressive re-induction of a-helical elements, a remarkable increase of the tryptophan fluorescence and a loss of enzyme activity. These results indicate that calcium ions in Euphorbia peroxidase play an essential role in maintaining the hydrophobic interactions on the protein structure preserving enzymatic activity.
The Journal of Organic Chemistry, Oct 1, 2010
A very efficient three-component synthesis of a series of syn α-hydroxy-β-amino esters, obtained ... more A very efficient three-component synthesis of a series of syn α-hydroxy-β-amino esters, obtained in high diastereoselection and yield, was realized starting from an aldehyde, benzylamine, and the ketene silyl acetals derived from Ley's lactones. The synthetic protocol was optimized and the above compounds were obtained without the isolation of intermediates. The origin of the observed diastereoselection was investigated through a computational model of the key reaction step.
The journal of physical chemistry. B, Jan 5, 2015
The mechanisms behind the propensity of chiral constrained Cα-tetrasubstituted amino acids (cCTAA... more The mechanisms behind the propensity of chiral constrained Cα-tetrasubstituted amino acids (cCTAAs) to induce one particular helical screw sense, when included in the Ac-Aib2-cCTAA-Aib2-NHMe peptide model, were studied through replica exchange molecular dynamics, potential of mean force, and quantum theory of atoms in molecules calculations. We observed that cCTAAs exert their effect on helical screw sense selectivity through the positioning of the side chain to generate steric hindrance in either the (-x, +y, +z) or (+x, +y, -z) sectors of a right-handed 3D Cartesian space, where the z axis corresponds to the axis of the helix and the Cα lies on the +y semiaxis (0, +y, 0). The different strengthening of the noncovalent interactions, also comprising C-H···O interactions, exerted by the cCTAA in the right-handed or left-handed helix was also found important to define the preference of a cCTAA for a particular helix screw sense.
Journal of Alloys and Compounds, 2013
ABSTRACT Ag and Cu powders with selected particle size have been synthesized by chemical solution... more ABSTRACT Ag and Cu powders with selected particle size have been synthesized by chemical solution methods, and employed to prepare Ag50Cu50 powder mixtures with total surface area known. Their mechanical processing induced the formation of Ag- and Cu-rich solid solutions at rates increasing with the total surface area. This can be ascribed to an extension of the mutual solubility limits, and to a simultaneous increase of the total amount of powders participating in dissolution processes at each collision. (c) 2013 Elsevier B.V. All rights reserved.
Viene presentato in questo articolo un lavoro svolto presso l'Istituto di Chimica Organica &... more Viene presentato in questo articolo un lavoro svolto presso l'Istituto di Chimica Organica "Alessandro Marchesini" riguardante la valutazione in silico di ammidi dell'acido 2-piridin acetico come inibitori del recettore tirosin chinasico EGFR. La ricerca è stata sviluppata utilizzando i supercalcolatori del CILEA.
Journal of Alloys and Compounds, 2013
ABSTRACT We have addressed a new study by mechanical alloying on the nominally immiscible Cu50Fe5... more ABSTRACT We have addressed a new study by mechanical alloying on the nominally immiscible Cu50Fe50 system with the aim of relating the solid state transformation process, with formation of a disordered unstable solid solution having the face centered cubic habit, to parameters reflecting the impulsive, discontinuous nature of the process. The milling set-up, tools and powder were adjusted in order to ensure completely anelastic hits. Phase analysis, structure and microstructure parameters of such powder system have been followed accurately in the course of the kinetics by X-ray Diffraction using the Rietveld method. The experimental kinetics data points of the amount of transformed solid solution show a typical sigmoidal behavior. It was assumed that dissolution only occurs in the volumes of material that have undergone the necessary critical loading conditions, which is accounted by a discrete series expansion. The mass fraction effectively processed at each collision can be regarded as an apparent rate constant for the microstructural refinement and phase transformation processes. Analysis of model curves fitting the experimental data suggests that it takes up an average of 6 impacts of coupled powder particles to drive the system to the new unstable nano-crystalline state.
Abstract: Recentemente è stato riportato come o-tiochinoni sostituiti possano reagire con 1, 3 di... more Abstract: Recentemente è stato riportato come o-tiochinoni sostituiti possano reagire con 1, 3 dieni aciclici e ciclici in reazioni di cicloaddizione secondo un meccanismo di tipo [2+ 4] o [4+ 2](Schema 1). 1 I risultati sperimentali mostrano che, a seconda della struttura dei reagenti e delle condizioni di reazione adottate, è possibile orientare la reazione verso il primo o il secondo meccanismo. Con l'obiettivo di comprendere i motivi alla base del comportamento osservato, abbiamo intrapreso uno studio computazionale a livello DFT. ...
Abstract: Mono-ortho-thioquinones, of general formula 1, can be generate under very mild conditio... more Abstract: Mono-ortho-thioquinones, of general formula 1, can be generate under very mild conditions by reacting the corresponding ortho-hydroxythiophthalimides 2 with bases.[1] Species 1, generate in situ, can be trapping through cycloaddition reactions with 1, 3-dienes. This chemistry allowed us to study in detail the reactivity of thioquinones 1 and to demonstrate their double behaviour as hetero dienophiles, across the carbon-sulfur double bond, to give the spiro derivates 4 and as hetero dienes leading to the formation of the ...
European Journal of Medicinal Chemistry
5-Sulfanyl-3-alkylaminoisothiazole dioxide derivatives have been identified as a new class of pot... more 5-Sulfanyl-3-alkylaminoisothiazole dioxide derivatives have been identified as a new class of potent inhibitors of rat aortic myocite proliferation. They were prepared by applying a simple methodology able to introduce a heteroatom on C-5 of the 3-alkylaminoisothiazole dioxide system. 3-Aminosubstituted-5-chloroisothiazole dioxides react smoothly not only with S-nucleophiles but also with N-and O-nucleophiles affording the corresponding 5-heterosubstituted isothiazole dioxides through an addition-elimination reaction. The behavior of 3-alkylamino-4bromo-isothiazole 1,1-dioxide with S-, N-and O-nucleophiles affording the same products has also been described. On the contrary, the 3amino-4,5-unsubstituted isothiazole dioxide system reacts easily only with sulfur nucleophiles affording the corresponding 4,5-dihydro-5-sulfanylderivatives through a simple Michael addition reaction.
The Journal of Organic Chemistry, 2015
A new α,α-disubstituted constrained glutamine analogue has been designed to decorate gold nanopar... more A new α,α-disubstituted constrained glutamine analogue has been designed to decorate gold nanoparticles and to induce a 310-helix when inserted in peptides. Using an efficient "one-pot" asymmetric Schmidt reaction between 4-disubstituted-cyclohexanone and hydroxyalkylazides, 1H-azepine-2-oxo-5-amino-5-carboxylic acid was prepared. The main (R) isomer was inserted at the N-terminus in a very short peptide sequence (i.e., PhCO-(R)-Oxo-Azn-l-Ala-Aib-l-AlaNHMe) and a stable 310-helix conformation was obtained, as verified by both NMR experiments and molecular dynamics (MD) simulations. Finally, the presence of the hydroxyl chain at the nitrogen atom of the ring allowed for the preparation of covered chiral gold nanoparticles.
Chem. Commun., 2015
Vibrational circular dichroism, VCD, gives evidence that the carbon monoxide chromophore in a het... more Vibrational circular dichroism, VCD, gives evidence that the carbon monoxide chromophore in a heteroleptic cyclopentadienyl Ru(ii)-carbonyl complex is very sensitive to the chirality of the metal centre and becomes an excellent probe to define the configuration of chiral metal complexes.
RSC Adv., 2015
Two model peptides containing the 3-benzylsulfanylnorbornene amino acid (NRB) was prepared. Theor... more Two model peptides containing the 3-benzylsulfanylnorbornene amino acid (NRB) was prepared. Theoretical calculations, spectroscopic and X-ray analyses confirmed that both NRB enantiomers possess a strong right-handed helicogenic effect.
Propellants, Explosives, Pyrotechnics, 2014
ABSTRACT Consolidated magnesium/poly[bis(2,2,2-trifluoroethoxy)phosphazene] (MPZ) pyrolants displ... more ABSTRACT Consolidated magnesium/poly[bis(2,2,2-trifluoroethoxy)phosphazene] (MPZ) pyrolants display a stable combustion regime between ξ(Mg) 30–83 wt-%. The combustion rate increases with increasing magnesium content. Mixtures containing between 15–29 wt-% Mg do ignite with a butane torch but extinguish rapidly thereafter. The combustion flames for each stoichiometric range exhibit particular features such as luminous carbon particles, after burn luminescence of Mg and burning Mg-rich ejecta. UV/Vis spectra of the combustion flames show a distinct continuum superimposed from signals for transient CF2, Mg, MgF, MgO, P2+, PH, PN, and PO. The thermochemical calculation using NASA-CEA indicate the highest adiabatic temperatures 1889 K at ξ(Mg)=35 wt-%. The aerobic combustion of MPZ yields similar temperatures as common magnesium/polytetrafluoroethylene pyrolants.
Synlett, 2012
Abstract A series of pentyl-sulfonyl amidines was obtained using a multicomponent synthesis proce... more Abstract A series of pentyl-sulfonyl amidines was obtained using a multicomponent synthesis process. The rearrangement of unstable tosylazide-cyclopentanonenamine cycloadducts yielded a diazoalkane intermediate. This primary, unstable reaction product showed good reactivity with certain acid compounds in order to form the corresponding derivatives.
Biochimica Et Biophysica Acta Proteins and Proteomics, Sep 11, 2014
The Maf protein family belongs to the activator protein 1 (AP-1) superfamily of transcription fac... more The Maf protein family belongs to the activator protein 1 (AP-1) superfamily of transcription factors that bind specific DNA target sequences through a basic region and exploit a leucine zipper (LZ) motif for protein-protein interactions leading to homo- or hetero-dimerization. Mafs unique DNA-binding domain contains a highly conserved extended homology region (EHR) that allows to recognize longer DNA sequences than other basic leucine zipper (bZIP) transcription factors. Inspired by the fact that overexpression of Mafs is observed in about 50% of cases of multiple myeloma, a hematological malignant disorder, we undertook a peptide inhibitor approach. The LZ domain of c-Maf, one of large Mafs, was produced by solid phase peptide synthesis. We characterized its secondary structure and dimerization properties, and found that dimerization and folding events are strictly coupled. Moreover, potential peptidic c-Maf dimerization inhibitors were computationally designed and synthesized. These compounds were demonstrated by circular dichroism (CD) spectroscopy and MALDI-TOF mass spectrometry to bind to c-Maf LZ monomers, to drive folding of their partially disordered structure and to efficiently compete with dimerization, suggesting a way for interfering with the function of c-Maf and, more generally, of intrinsically disordered proteins, till now considered undruggable targets.
Cheminform, Feb 22, 2011
AbstractA highly diastereoselective and very efficient method to prepare title compounds is repor... more AbstractA highly diastereoselective and very efficient method to prepare title compounds is reported.
Journal of Protein Chemistry, Nov 18, 2008
Activity assays, conformational changes and transitional switches between secondary structures of... more Activity assays, conformational changes and transitional switches between secondary structures of a peroxidase from Euphorbia characias were studied in the presence of trifluoroethanol and in the presence or absence of calcium ions. The addition of trifluoroethanol up to 10-20% first induced a drastic decrease of a-helix content followed by an increase of tryptophan fluorescence emission intensity, a progressive re-induction of the formation of a-helical elements concomitant with loss of enzyme activity. In the presence of calcium ions, the fluorescence of the enzyme almost remained unchanged in the trifluoroethanol concentration range 5-20%. Further increase in trifluoroethanol concentration led to a protein structure characterized by a progressive re-induction of a-helical elements, a remarkable increase of the tryptophan fluorescence and a loss of enzyme activity. These results indicate that calcium ions in Euphorbia peroxidase play an essential role in maintaining the hydrophobic interactions on the protein structure preserving enzymatic activity.
The Journal of Organic Chemistry, Oct 1, 2010
A very efficient three-component synthesis of a series of syn α-hydroxy-β-amino esters, obtained ... more A very efficient three-component synthesis of a series of syn α-hydroxy-β-amino esters, obtained in high diastereoselection and yield, was realized starting from an aldehyde, benzylamine, and the ketene silyl acetals derived from Ley's lactones. The synthetic protocol was optimized and the above compounds were obtained without the isolation of intermediates. The origin of the observed diastereoselection was investigated through a computational model of the key reaction step.
The journal of physical chemistry. B, Jan 5, 2015
The mechanisms behind the propensity of chiral constrained Cα-tetrasubstituted amino acids (cCTAA... more The mechanisms behind the propensity of chiral constrained Cα-tetrasubstituted amino acids (cCTAAs) to induce one particular helical screw sense, when included in the Ac-Aib2-cCTAA-Aib2-NHMe peptide model, were studied through replica exchange molecular dynamics, potential of mean force, and quantum theory of atoms in molecules calculations. We observed that cCTAAs exert their effect on helical screw sense selectivity through the positioning of the side chain to generate steric hindrance in either the (-x, +y, +z) or (+x, +y, -z) sectors of a right-handed 3D Cartesian space, where the z axis corresponds to the axis of the helix and the Cα lies on the +y semiaxis (0, +y, 0). The different strengthening of the noncovalent interactions, also comprising C-H···O interactions, exerted by the cCTAA in the right-handed or left-handed helix was also found important to define the preference of a cCTAA for a particular helix screw sense.
Journal of Alloys and Compounds, 2013
ABSTRACT Ag and Cu powders with selected particle size have been synthesized by chemical solution... more ABSTRACT Ag and Cu powders with selected particle size have been synthesized by chemical solution methods, and employed to prepare Ag50Cu50 powder mixtures with total surface area known. Their mechanical processing induced the formation of Ag- and Cu-rich solid solutions at rates increasing with the total surface area. This can be ascribed to an extension of the mutual solubility limits, and to a simultaneous increase of the total amount of powders participating in dissolution processes at each collision. (c) 2013 Elsevier B.V. All rights reserved.
Viene presentato in questo articolo un lavoro svolto presso l'Istituto di Chimica Organica &... more Viene presentato in questo articolo un lavoro svolto presso l'Istituto di Chimica Organica "Alessandro Marchesini" riguardante la valutazione in silico di ammidi dell'acido 2-piridin acetico come inibitori del recettore tirosin chinasico EGFR. La ricerca è stata sviluppata utilizzando i supercalcolatori del CILEA.
Journal of Alloys and Compounds, 2013
ABSTRACT We have addressed a new study by mechanical alloying on the nominally immiscible Cu50Fe5... more ABSTRACT We have addressed a new study by mechanical alloying on the nominally immiscible Cu50Fe50 system with the aim of relating the solid state transformation process, with formation of a disordered unstable solid solution having the face centered cubic habit, to parameters reflecting the impulsive, discontinuous nature of the process. The milling set-up, tools and powder were adjusted in order to ensure completely anelastic hits. Phase analysis, structure and microstructure parameters of such powder system have been followed accurately in the course of the kinetics by X-ray Diffraction using the Rietveld method. The experimental kinetics data points of the amount of transformed solid solution show a typical sigmoidal behavior. It was assumed that dissolution only occurs in the volumes of material that have undergone the necessary critical loading conditions, which is accounted by a discrete series expansion. The mass fraction effectively processed at each collision can be regarded as an apparent rate constant for the microstructural refinement and phase transformation processes. Analysis of model curves fitting the experimental data suggests that it takes up an average of 6 impacts of coupled powder particles to drive the system to the new unstable nano-crystalline state.
Abstract: Recentemente è stato riportato come o-tiochinoni sostituiti possano reagire con 1, 3 di... more Abstract: Recentemente è stato riportato come o-tiochinoni sostituiti possano reagire con 1, 3 dieni aciclici e ciclici in reazioni di cicloaddizione secondo un meccanismo di tipo [2+ 4] o [4+ 2](Schema 1). 1 I risultati sperimentali mostrano che, a seconda della struttura dei reagenti e delle condizioni di reazione adottate, è possibile orientare la reazione verso il primo o il secondo meccanismo. Con l'obiettivo di comprendere i motivi alla base del comportamento osservato, abbiamo intrapreso uno studio computazionale a livello DFT. ...
Abstract: Mono-ortho-thioquinones, of general formula 1, can be generate under very mild conditio... more Abstract: Mono-ortho-thioquinones, of general formula 1, can be generate under very mild conditions by reacting the corresponding ortho-hydroxythiophthalimides 2 with bases.[1] Species 1, generate in situ, can be trapping through cycloaddition reactions with 1, 3-dienes. This chemistry allowed us to study in detail the reactivity of thioquinones 1 and to demonstrate their double behaviour as hetero dienophiles, across the carbon-sulfur double bond, to give the spiro derivates 4 and as hetero dienes leading to the formation of the ...
European Journal of Medicinal Chemistry
5-Sulfanyl-3-alkylaminoisothiazole dioxide derivatives have been identified as a new class of pot... more 5-Sulfanyl-3-alkylaminoisothiazole dioxide derivatives have been identified as a new class of potent inhibitors of rat aortic myocite proliferation. They were prepared by applying a simple methodology able to introduce a heteroatom on C-5 of the 3-alkylaminoisothiazole dioxide system. 3-Aminosubstituted-5-chloroisothiazole dioxides react smoothly not only with S-nucleophiles but also with N-and O-nucleophiles affording the corresponding 5-heterosubstituted isothiazole dioxides through an addition-elimination reaction. The behavior of 3-alkylamino-4bromo-isothiazole 1,1-dioxide with S-, N-and O-nucleophiles affording the same products has also been described. On the contrary, the 3amino-4,5-unsubstituted isothiazole dioxide system reacts easily only with sulfur nucleophiles affording the corresponding 4,5-dihydro-5-sulfanylderivatives through a simple Michael addition reaction.
The Journal of Organic Chemistry, 2015
A new α,α-disubstituted constrained glutamine analogue has been designed to decorate gold nanopar... more A new α,α-disubstituted constrained glutamine analogue has been designed to decorate gold nanoparticles and to induce a 310-helix when inserted in peptides. Using an efficient "one-pot" asymmetric Schmidt reaction between 4-disubstituted-cyclohexanone and hydroxyalkylazides, 1H-azepine-2-oxo-5-amino-5-carboxylic acid was prepared. The main (R) isomer was inserted at the N-terminus in a very short peptide sequence (i.e., PhCO-(R)-Oxo-Azn-l-Ala-Aib-l-AlaNHMe) and a stable 310-helix conformation was obtained, as verified by both NMR experiments and molecular dynamics (MD) simulations. Finally, the presence of the hydroxyl chain at the nitrogen atom of the ring allowed for the preparation of covered chiral gold nanoparticles.
Chem. Commun., 2015
Vibrational circular dichroism, VCD, gives evidence that the carbon monoxide chromophore in a het... more Vibrational circular dichroism, VCD, gives evidence that the carbon monoxide chromophore in a heteroleptic cyclopentadienyl Ru(ii)-carbonyl complex is very sensitive to the chirality of the metal centre and becomes an excellent probe to define the configuration of chiral metal complexes.
RSC Adv., 2015
Two model peptides containing the 3-benzylsulfanylnorbornene amino acid (NRB) was prepared. Theor... more Two model peptides containing the 3-benzylsulfanylnorbornene amino acid (NRB) was prepared. Theoretical calculations, spectroscopic and X-ray analyses confirmed that both NRB enantiomers possess a strong right-handed helicogenic effect.
Propellants, Explosives, Pyrotechnics, 2014
ABSTRACT Consolidated magnesium/poly[bis(2,2,2-trifluoroethoxy)phosphazene] (MPZ) pyrolants displ... more ABSTRACT Consolidated magnesium/poly[bis(2,2,2-trifluoroethoxy)phosphazene] (MPZ) pyrolants display a stable combustion regime between ξ(Mg) 30–83 wt-%. The combustion rate increases with increasing magnesium content. Mixtures containing between 15–29 wt-% Mg do ignite with a butane torch but extinguish rapidly thereafter. The combustion flames for each stoichiometric range exhibit particular features such as luminous carbon particles, after burn luminescence of Mg and burning Mg-rich ejecta. UV/Vis spectra of the combustion flames show a distinct continuum superimposed from signals for transient CF2, Mg, MgF, MgO, P2+, PH, PN, and PO. The thermochemical calculation using NASA-CEA indicate the highest adiabatic temperatures 1889 K at ξ(Mg)=35 wt-%. The aerobic combustion of MPZ yields similar temperatures as common magnesium/polytetrafluoroethylene pyrolants.