A5030558940- Influenza Virus Research Studies
- Proteoglycans and glycosaminoglycans research
- Glycosylation and Glycoproteins Research
- SARS-CoV-2 and COVID-19 Research
- Carbohydrate Chemistry and Synthesis
- Polymer Surface Interaction Studies
- Protein Structure and Dynamics
- Heparin-Induced Thrombocytopenia and Thrombosis
- COVID-19 Clinical Research Studies
- RNA and protein synthesis mechanisms
- Force Microscopy Techniques and Applications
- Monoclonal and Polyclonal Antibodies Research
- Bacteriophages and microbial interactions
- interferon and immune responses
- Drug Solubulity and Delivery Systems
- Concrete and Cement Materials Research
- Blood properties and coagulation
- Microfluidic and Capillary Electrophoresis Applications
- Material Dynamics and Properties
- Platelet Disorders and Treatments
- Rheology and Fluid Dynamics Studies
- Nanofabrication and Lithography Techniques
- Fibroblast Growth Factor Research
- Advanced Chemical Physics Studies
- COVID-19 Impact on Reproduction
Istituto di Ricerche Chimiche e Biochimiche G. Ronzoni
2013-2024
Politecnico di Milano
2004-2008
University College Dublin
2005
University of Insubria
2000
The dependence of development and homeostasis in animals on the interaction hundreds extracellular regulatory proteins with peri- glycosaminoglycan heparan sulfate (HS) is exploited by many microbial pathogens as a means adherence invasion. Heparin, widely used anticoagulant drug, structurally similar to HS common experimental proxy. Exogenous heparin prevents infection range viruses, including S-associated coronavirus isolate HSR1. Here, we show that inhibits severe acute respiratory...
Abstract Many pathogens take advantage of the dependence host on interaction hundreds extracellular proteins with glycosaminoglycans heparan sulphate to regulate homeostasis and use as a means adhere gain access cells. Moreover, mucosal epithelia such that respiratory tract are protected by layer mucin polysaccharides, which usually sulphated. Consequently, polydisperse, natural products allied polysaccharide, heparin have been found be involved prevent infection range viruses including...
Abstract The dependence of the host on interaction hundreds extracellular proteins with cell surface glycosaminoglycan heparan sulphate (HS) for regulation homeostasis is exploited by many microbial pathogens as a means adherence and invasion. closely related polysaccharide heparin, widely used anticoagulant drug, which structurally similar to HS common experimental proxy, can be expected mimic properties HS. Heparin prevents infection range viruses if added exogenously, including...
We present the results of computer simulations model polymer networks containing stiff and roughly spherical colloidal particles at 20% volume fraction. employ coarse-grained "dissipative particle dynamics" (DPD). The filler may be either well dispersed or aggregated, strength their interaction can tuned by changing parameters polymer−filler nonbonded potentials. By performing nonequilibrium molecular dynamics simulations, we are able to probe directly viscoelastic behavior composites under...
SARS-CoV-2 has rapidly spread throughout the world's population since its initial discovery in 2019. The virus infects cells via a glycosylated spike protein located on surface. primarily binds to angiotensin-converting enzyme-2 (ACE2) receptor, using glycosaminoglycans (GAGs) as co-receptors. Here, we performed bioinformatics and molecular dynamics simulations of investigate existence additional GAG binding sites receptor-binding domain (RBD), separate from previously reported...
Cyclodextrins (CDs) are cyclic oligosaccharides able to form noncovalent water-soluble complexes useful in many different applications for the solubilization, delivery, and greater bioavailability of hydrophobic drugs. The complexation 5-fluorouracil (5-FU) with natural or synthetic cyclodextrins permits solubilization this poorly soluble anticancer drug. In theoretical work, between β-CD 5-FU investigated using molecular mechanics (MM) dynamics (MD) simulations water. inclusion formed...
Single-chain simulations of densely branched comb polymers, or "molecular bottle-brushes" with side-chains attached to every (or second) backbone monomer, were carried out by off-lattice Monte Carlo technique. A coarse-grained model, described hard spheres connected harmonic springs, was employed. Backbone lengths up 100 units considered, and compared the corresponding linear chains. The molecular size investigated as a function its length at fixed arm size, length. apparent swelling...
The 3-O-sulfation of N-sulfated glucosamine is the last event in biosynthesis heparin/heparan sulfate, giving rise to antithrombin-binding pentasaccharide sequence AGA*IA, which largely associated with antithrombotic activity these molecules. aim present study was structural and biochemical characterization a previously unreported AGA*IA*-containing octasaccharide isolated from very-low-molecular-mass heparin semuloparin, both residues moiety located at non-reducing end bear 3-O-sulfate...
Differential interactions between influenza A virus protein hemagglutinin (HA) and α2→3 (avian) or α2→6 (human) sialylated glycan receptors play an important role in governing host specificity adaptation of the virus. Previous analysis HA–glycan with trisaccharides showed that, addition to terminal sialic acid linkage, conformation topology glycans, while they are bound HA, key factors regulating these interactions. Here, solution dynamics two representative avian human pentasaccharide...
Single-chain Monte Carlo simulations were carried out, in continuous space, of polymers with various topologies (branched and linear) the good solvent. Using an inherently flexible bead-and-spring model, backbone linear either or dendritic side-groups attached was found to be elongated, indicative induced stiffness. This "topological stiffness" compared "intrinsic semiflexible terms observables. Semiflexible comb polymers, which contained both types stiffness, also considered.
Terminal 1,6-anhydro-aminosugars (1,6-anAS) are typical structural moieties of enoxaparin, a low-molecular-weight heparin (LMWH) widely used for prevention and treatment thrombotic disorders. In the enoxaparin manufacturing process, these modified amino sugars formed during β-eliminative cleavage heparin. To investigate effect terminal anAS on antithrombin (AT) binding inhibition factor Xa (FXa), two octasaccharides containing AT-binding pentasaccharide sequences were isolated from...
Two years since the outbreak of novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome 2) pandemic, there remain few clinically effective drugs to complement vaccines. One is anticoagulant, heparin, which in 2004 was found able inhibit invasion SARS-CoV (CoV-1) and has been employed during current pandemic prevent thromboembolic complications moderate potentially damaging inflammation. Heparin also shown experimentally attachment infection susceptible cells. At high therapeutic...
Abstract The dependence of the host on interaction hundreds extracellular proteins with cell surface glycosaminoglycan heparan sulphate (HS) for regulation homeostasis is exploited by many microbial pathogens as a means adherence and invasion. closely related polysaccharide heparin, widely used anticoagulant drug, which structurally similar to HS common experimental proxy, can be expected mimic properties HS. Heparin prevents infection range viruses when added exogenously, including...
The potential energy curve of e+LiH has been computed by means diffusion Monte Carlo using explicitly correlated trial wave functions. This allows us to compute the adiabatic total and binding energies vibrational spectrum e+LiH, positron affinity LiH. Using these results, we discuss possibility detect spectroscopically in gas phase, order have first direct observation a positron-containing system.
Abstract Some intrinsic properties of biomaterials are calculated with atomistic computer simulations through energy minimizations and molecular dynamics methods. The mechanical bulk polymers such as poly(vinyl alcohol) poly(ethylene terephthalate) obtained in terms the Young's modulus, shear moduli, Poisson ratio below glass transition temperature. values apply to an ideal, defect‐free sample, therefore, they correspond theoretical upper limit for behavior these materials. surface hydration...
Heparanase is the only known endoglycosidase able to cleave heparan sulfate. Roneparstat and necuparanib, heparanase inhibitors obtained from heparin currently being tested in man as a potential drugs against cancer, contain their structure glycol-split uronic acid moieties probably responsible for strong inhibitory activity. We describe here total chemical synthesis of trisaccharide GlcNS6S-GlcA-1,6anGlcNS (1) its (gs) counterpart GlcNS6S-gsGlcA-1,6anGlcNS (2) glucose. As expected,...
Abstract Cyclodextrins (CDs) are natural macrocyclic oligosaccharides able to solubilize hydrophobic drugs in water improving their bioavailability, thanks favorable noncovalent interactions particularly cavity. Using a simulation protocol proposed previous work, this theoretical study based on Molecular Mechanics (MM) and Dynamics (MD) methods, inclusion complexes between β ‐cyclodextrin 5‐Fluorouracil (5‐FU) investigated. 5‐FU is an anticancer drug hardly soluble used for more than 50...
Infection of host cells by SARS-CoV-2 begins with recognition the virus S (spike) protein cell surface heparan sulfate (HS), tethering to extracellular matrix environment, and causing subunit S1-RBD undergo a conformational change into 'open' conformation. These two events promote binding angiotensin converting enzyme 2 (ACE2) receptor, preliminary step toward viral-cell membrane fusion. Combining ligand-based NMR spectroscopy molecular dynamics, oligosaccharide analogues were used explore...
The glycan receptor binding and specificity of influenza A viral hemagglutinin (HA) are critical for virus infection transmission in humans. However, ambiguities the interpretation from human- avian-adapted viruses have prevented an understanding its relationship with aerosol transmissibility, exclusive property human-adapted viruses. previous conformational study, which we performed, indicated that human avian receptors sample distinct conformations solution. On basis detailed nuclear...
Abstract The glycosaminoglycan (GAG) class of polysaccharides are utilised by a plethora microbial pathogens as receptors for adherence and invasion. GAG heparin prevents infection range viruses when added exogenously, including the S-associated coronavirus strain HSR1 more recently we have demonstrated that can block cellular invasion SARS-CoV-2. Heparin has found widespread clinical use anticoagulant drug this molecule is routinely used proxy GAG, heparan sulphate (HS), structural analogue...
Avian influenza A viruses, which can also propagate between humans, present serious pandemic threats, particularly in Asia. The specificity (selectivity) of interactions the recognition protein hemagglutinin (HA) virus capsid and glycoconjugates host cells contributes to efficient spread by aerosol humans. Some avian origin such as H1N1 (South Carolina 1918), have improved their selectivity for human receptors mutation HA receptor binding site, generate viruses. Molecular details dynamics...
Abstract Heparin is a highly sulfated glycosaminoglycan (GAG) of natural origin used as an anticoagulant and antithrombotic drug. These properties are principally based on the binding activation antithrombin (AT) through pentasaccharide sequence GlcNAc/NS,6S‐GlcA‐GlcNS,3,6S‐IdoA2S‐GlcNS,6S (AGA*IA). Literature data show that population 2 S 0 ring conformation 2‐ O ‐sulfo‐α‐ l ‐iduronic acid (IdoA2S) motif correlates with affinity AT. It was recently demonstrated two synthetic...
The heparan sulfate mimetic PI-88 is a complex mixture of sulfated oligosaccharides with anti-metastatic and anti-angiogenic activity due to its potent inhibition heparanase sulfate-dependent angiogenic growth factors. It was recently in Phase III clinical trials for postresection hepatocellular carcinoma. major oligosaccharide constituents were prepared the first time by sulfonation individually purified phosphorylated isolated from precursor. components subjected detailed 1D 2D NMR...
The interaction of heparin with antithrombin (AT) involves a specific sequence corresponding to the pentasaccharide GlcNAc/NS6S-GlcA-GlcNS3S6S-IdoA2S-GlcNS6S (AGA*IA). Recent studies have revealed that two AGA*IA-containing hexasaccharides, which differ in sulfation degree iduronic acid unit, exhibit similar binding AT, albeit different affinities. However, lack experimental data concerning molecular contacts between these ligands and amino acids within protein-binding site prevents detailed...