A5049468982- Receptor Mechanisms and Signaling
- Nicotinic Acetylcholine Receptors Study
- Neuropeptides and Animal Physiology
- Cholinesterase and Neurodegenerative Diseases
- Synthesis and Biological Evaluation
- Neuroscience and Neuropharmacology Research
- Pharmacological Receptor Mechanisms and Effects
- Analytical Chemistry and Chromatography
- Ion channel regulation and function
- Bioactive Compounds and Antitumor Agents
- Chemical synthesis and alkaloids
- Chemical Synthesis and Analysis
- Biochemical effects in animals
- Advancements in Transdermal Drug Delivery
- Organic Chemistry Cycloaddition Reactions
- Free Radicals and Antioxidants
- Carbohydrate Chemistry and Synthesis
- Synthesis and Reactions of Organic Compounds
- Vagus Nerve Stimulation Research
- Computational Drug Discovery Methods
- Synthesis and biological activity
- Protein Kinase Regulation and GTPase Signaling
- Pharmacological Effects and Assays
- Antibiotics Pharmacokinetics and Efficacy
- Asymmetric Synthesis and Catalysis
University of Milan
2016-2025
University of North Carolina at Chapel Hill
2017
University of Würzburg
2005-2017
University of Bonn
2005-2017
Ospedale San Pietro Fatebenefratelli
2017
Mylan (South Africa)
2017
University of Parma
2005
Istituto di Farmacologia Traslazionale
1999
Istituto di Chimica Biomolecolare
1992
Selective modulation of cell function by G protein-coupled receptor (GPCR) activation is highly desirable for basic research and therapy but difficult to achieve. We present a novel strategy toward this goal using muscarinic acetylcholine receptors as model. The five subtypes bind their physiological transmitter in the conserved orthosteric site within transmembrane domains receptors. Orthosteric activators have no binding selectivity poor signaling specificity. There less well allosteric at...
Seven transmembrane helical receptors (7TMRs) modulate cell function via different types of G proteins, often in a ligand-specific manner. Class A 7TMRs harbour allosteric vestibules the entrance their ligand-binding cavities, which are focus current drug discovery. However, biological remains enigmatic. Here we present new strategy for probing and manipulating conformational transitions vestibule label-free using M(2) acetylcholine receptor as paradigm. We designed dualsteric agonists...
G protein-coupled receptors constitute the largest family of membrane and modulate almost every physiological process in humans. Binding agonists to induces a shift from inactive active receptor conformations. Biophysical studies dynamic equilibrium suggest that portion can remain states even presence saturating concentrations agonist protein mimetic. However, molecular details agonist-bound are poorly understood. Here we use model bitopic orthosteric/allosteric (i.e. dualsteric) for...
Background and Purpose Artificial agonists may have higher efficacy for receptor activation than the physiological agonist. Until now, such ‘superagonism’ has rarely been reported GPCRs . Iperoxo is an extremely potent muscarinic We hypothesized that iperoxo a ‘superagonist’. Experimental Approach Signalling of newly synthesized structural analogues was compared with ACh at label‐free M 2 receptors applying whole cell dynamic mass redistribution, measurement G ‐protein activation, evaluation...
Background: Oligodendrocytes (OLs) are highly sensitive to oxygen-reactive species produced during neuro-inflammation. α7 nAChRs expressed in glial cells where they can modulate several physiological and pathological functions. OL progenitors (OPCs) respond cholinergic stimuli via muscarinic receptors that mainly involved the modulation of their proliferation. Differently, role nicotinic receptors, particular nAChRs, has been poorly investigated. In this study, we evaluated expression a...
In the pressing quest of novel treatments for chronic pain, α7 nAChR silent agonists show efficacy as anti-inflammatory modulators and represent a promising strategy. Recent findings reveal that sulfonium ion can replace quaternary ammonium nitrogen an alternative pharmacophore activation. This study reports design, synthesis, electrophysiological evaluation new series sulfonium-based derivatives inspired by archetypal agonist NS6740. Our identify NSS-9 effectively alleviates inflammatory...
A novel series of muscarinic receptor ligands the hexamethonio-type was prepared which contained, on one side, phthalimidopropane or 1,8-naphthalimido-2,2-dimethylpropane moiety typical for subtype selective allosteric antagonists and, other, acetylenic fragment nonselective orthosteric agonists oxotremorine, oxotremorine-M, and related agonists. Binding experiments in M2 receptors using [3H]N-methylscopolamine as an probe proved action both groups hybrids, 7a−10a 8b−10b. The difference...
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...
Purpuromycin (1) is an antibiotic with a broad spectrum of antimicrobial activity, encompassing bacteria, fungi, and protozoa, particularly those involved in vaginal infections. With the aim enhancing solubility reducing serum binding, chemical program modifications was undertaken on natural compound, new interesting series derivatives at naphthoquinone system synthesized evaluated as potential topical agents for In particular three semisynthetic derivatives, 7'-amino (8a), 7'-methylamino...
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...
l-Carnosine (β-Ala-l-His) and several other histidine-containing peptides, including two N-methylated forms on the imidazole ring (l-anserine l-balenine), derivatives modified carboxyl function (carcinine l-carnosinamide), analogues differing in length of N-terminal residue (l-homocarnosine Gly-l-His) N-acetyl derivatives, were investigated as activators four isoforms metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). The human hCA I, II, VA IX activated low to high micromolar range, with a...
Allosteric coupling describes a reciprocal process whereby G-protein-coupled receptors (GPCRs) relay ligand-induced conformational changes from the extracellular binding pocket to intracellular signaling surface. Therefore, GPCR activation is sensitive both type of ligand and protein. We hypothesized that ligand-specific allosteric may result in preferential (i.e., biased) engagement downstream effectors. However, structural basis underlying ligand-dependent control this essential mechanism...