A5013096980- Nicotinic Acetylcholine Receptors Study
- Receptor Mechanisms and Signaling
- Chemical Synthesis and Analysis
- Computational Drug Discovery Methods
- Neuroscience and Neuropharmacology Research
- Cholinesterase and Neurodegenerative Diseases
- Biochemical and Structural Characterization
- Antibiotic Resistance in Bacteria
- RNA and protein synthesis mechanisms
- Pharmacological Receptor Mechanisms and Effects
- Lipoproteins and Cardiovascular Health
- Crystallization and Solubility Studies
- Synthesis and Biological Evaluation
- Botanical Research and Chemistry
- Analytical Chemistry and Chromatography
- X-ray Diffraction in Crystallography
- Immune Response and Inflammation
- Molecular spectroscopy and chirality
- Bacterial biofilms and quorum sensing
- Ion channel regulation and function
- Click Chemistry and Applications
- Trypanosoma species research and implications
- Chemokine receptors and signaling
- Malaria Research and Control
- Advanced Glycation End Products research
University of Milan
2015-2024
Mylan (South Africa)
2015-2016
Lundbeck (Denmark)
2005
University of Florence
2005
ETH Zurich
2005
University of Pavia
2004
Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been recently identified as a new useful target for hypercholesterolemia treatment. This work demonstrates that natural peptides, deriving from the hydrolysis of lupin protein and absorbable at intestinal level, are able to inhibit protein-protein interaction between PCSK9 low density lipoprotein receptor (LDLR). In order sort out best potential inhibitors among these refined in silico model PCSK9/LDLR was developed. Docking,...
A homeostatic concentration of glutamate in the synaptic cleft ensures a correct signal transduction along neuronal network. An unbalance this can lead to death and severe neurodegenerative diseases such as Alzheimer's or Parkinson's. Glutamate transporters play crucial role respect because they are responsible for reuptake neurotransmitter from cleft, thus controlling concentration. Understanding molecular mechanism transporter provide possibility an exogenous control. Structural studies...
We report on a tetraimidazole-based β-strand minimalist peptidomimetic as novel inhibitor of LDLR–PCSK9 protein–protein interaction, promising target for hypercholesterolemia.
Chlorella pyrenoidosa (C. pyrenoidosa) is a microalgae species with remarkably high protein content that may potentially become source of hypotensive and hypoglycemic peptides. In this study, C. proteins were extracted hydrolyzed overnight pepsin trypsin final degrees hydrolysis 18.7% 35.5%, respectively. By LC-MS/MS, 47 valid peptides identified in the peptic hydrolysate (CP) 66 tryptic one (CT). At concentration 1.0 mg/mL, CP CT hydrolysates inhibit vitro angiotensin-converting enzyme...
Heteromeric nAChRs are pentameric cation channels, composed of combinations two or three α and β subunits, which play key physiological roles in the central peripheral nervous systems. The prototypical agonist nicotine acts intracellularly to upregulate many nAChR subtypes, a phenomenon that is thought contribute dependence cigarette smokers. α3β4 subtype has recently been genetically linked lung cancer; however, mode action on this receptor incompletely investigated. Here, using transfected...
Inflammation is a vital defense mechanism activated in response to injury or infection, which induces the release of cytokines and chemokines promote tissue repair. However, persistent inflammation may result development autoimmune diseases. During pathological conditions such as rheumatoid arthritis, HMGB1 kept its reduced isoform can complex with CXCL12 enhancing cell migration exacerbating immune responses. Small organic compounds selective for have been previously reported be able...
In this research, salicylic acid is proposed as an alternative biocide-free agent suitable for a preventive or integrative anti-biofilm approach. Salicylic has been proved to: (1) reduce bacterial adhesion up to 68.1 ± 5.6%; (2) affect biofilm structural development, reducing viable biomass by 97.0 0.7% and extracellular proteins polysaccharides 83.9 2.5% 49.5 5.5% respectively; (3) promote detachment 3.4 0.6-fold. Moreover, treated showed increased amount of intracellular (2.3 0.2-fold)...
Proprotein convertase subtilisin/kexin 9 (PCSK9) is responsible for the degradation of hepatic low-density lipoprotein receptor (LDLR), which in turn regulates circulating cholesterol (LDL-C) level. For this reason, PCSK9 inhibition, by small molecules or peptides, a validated therapeutic approach fighting hypercholesterolemia and cardiovascular diseases. In field, we have recently reported an imidazole-based peptidomimetic that has shown inhibitory activity micromolar range. Here, applying...
Bacterial biofilm is a major contributor to the persistence of infection and limited efficacy antibiotics. Antibiofilm molecules that interfere with lifestyle offer valuable tool in fighting bacterial pathogens. Ellagic acid (EA) natural polyphenol has shown attractive antibiofilm properties. However, its precise mode action remains unknown. Experimental evidence links NADH:quinone oxidoreductase enzyme WrbA formation, stress response, pathogen virulence. Moreover, demonstrated interactions...
α6β2∗ Nicotinic acetylcholine receptors are expressed in selected central nervous system areas, where they involved striatal dopamine (DA) release and its behavioral consequences, other still uncharacterized brain activities. selectively blocked by the α-conotoxins MII PIA, which bear a characteristic N- terminal amino acid tail [arginine (R), aspartic (D), proline (P)]. We synthesized group of PIA-related peptides R1 was mutated or RDP motif gradually removed. Binding DA assays native rat...
The fast and constant development of drug-resistant bacteria represents a serious medical emergence. To overcome this problem, the drugs with new structures modes action is urgently needed. In context, avibactam promising, innovative inhibitor beta-lactamases novel molecular structure compared to previously developed inhibitors, showing promising inhibitory activity toward significant number beta-lactamase enzymes. work, we studied, at atomistic level, mechanisms formation covalent complex...
P5 (LILPKHSDAD) is a hypocholesterolemic peptide from lupin protein with multi-target activity, since it inhibits both 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCoAR) and proprotein convertase subtilisin/kexin type-9 (PCSK9). This work shows that, during epithelial transport experiments, the metabolic transformation mediated by intestinal peptidases produces two main detected peptides, ILPKHSDAD (P5-frag) LPKHSDAD (P5-met), that P5-met are linearly absorbed differentiated human...
(1) Background: Proprotein convertase subtilisin/kexin 9 (PCSK9) is responsible for the degradation of hepatic low-density lipoprotein receptor (LDLR), which regulates circulating cholesterol level. In this field, we discovered natural peptides derived from lupin that showed PCSK9 inhibitory activity. Among these, most active peptide, known as P5 (LILPHKSDAD), reduced protein-protein interaction between and LDLR with an IC50 equals to 1.6 µM a dual hypocholesterolemic activity, since it...
A set of racemic spirocyclic quinuclidinyl-Δ(2)-isoxazoline derivatives was synthesized using a 1,3-dipolar cycloaddition-based approach. Target compounds were assayed for binding affinity toward rat neuronal homomeric (α7) and heteromeric (α4β2) nicotinic acetylcholine receptors. Δ(2) -Isoxazolines 3 (3-Br), 6 (3-OMe), 5 (3-Ph), 8 (3-OnPr), 4 (3-Me) the ligands with highest α7 subtype (K(i) values equal to 13.5, 14.2, 25.0, 71.6, 96.2 nM, respectively), showed excellent versus α4β2...
Abstract Herein we report the synthesis of a set constrained peptidomimetics endowed with an electrophilic vinyl ester warhead and structurally related to previously identified lead compound, potent irreversible inhibitor falcipain‐2 (FP‐2). FP‐2 is main hemoglobinase malaria parasite P. falciparum . The new compounds were evaluated for their inhibition against FP‐2, results rationalized on basis docking experiments. These studies underscore pivotal role both function at P1′ site...
Three different chiral piperazine-based scaffolds have been synthesized using a Ugi/cyclization strategy.
The inhibition of the PCSK9/LDLR protein-protein interaction is a promising strategy for developing new hypocholesterolemic agents. Familial hypercholesterolemia linked to specific PCSK9 mutations: D374Y most potent gain-of-function (GOF) mutation among clinically relevant ones. Recently, lupin peptide (T9) showed inhibitory effects on this mutant form, being also capable increase liver uptake low density lipoprotein cholesterol. In Letter, aiming improve potency peptide, T9 residues mainly...
The four stereoisomers of 5-(2-amino-2-carboxyethyl)-4,5-dihydroisoxazole-3-carboxylic acid(+)-4, (-)-4, (+)-5, and (-)-5 were prepared by stereoselective synthesis two pairs enantiomers, which subsequently resolved enzymatic procedures. These the bicyclic analogue 5-amino-4,5,6,6a-tetrahydro-3aH-cyclopenta[d]isoxazole-3,5-dicarboxylic acid (+)-2, (-)-2, (+)-3, (-)-3 tested at ionotropic metabotropic glutamate receptor subtypes. most potent NMDA antagonists [(+)-2, (+)-5] showed a...
Abstract A group of agonists for the α7 neuronal nicotinic acetylcholine receptors (nAChRs) was investigated, and their free energies binding Δ G bind were calculated by applying molecular mechanics Poisson–Boltzmann surface area (MM‐PBSA) approach. This method, based on dynamics simulations fully solvated protein–ligand complexes, allowed us to estimate contribution both polar nonpolar terms as well entropy overall energy binding. The results in a good agreement with experimentally...