A5025147752- Protein Degradation and Inhibitors
- Multiple Myeloma Research and Treatments
- Cancer-related gene regulation
- Advanced biosensing and bioanalysis techniques
- Wnt/β-catenin signaling in development and cancer
- Dendrimers and Hyperbranched Polymers
- Advanced Glycation End Products research
- Ubiquitin and proteasome pathways
- Microbial metabolism and enzyme function
- Click Chemistry and Applications
- Enzyme Production and Characterization
- RNA Research and Splicing
- Diet, Metabolism, and Disease
- RNA modifications and cancer
- Monoclonal and Polyclonal Antibodies Research
- Enzyme Structure and Function
- Protein Kinase Regulation and GTPase Signaling
- Polyoxometalates: Synthesis and Applications
- Toxin Mechanisms and Immunotoxins
- Microbial Metabolism and Applications
- Microbial Metabolic Engineering and Bioproduction
- HIV/AIDS drug development and treatment
- Protein Structure and Dynamics
- Chemical Synthesis and Analysis
- Biotin and Related Studies
University of Trento
2017-2024
Center for Nano Science and Technology
2015-2019
Italian Institute of Technology
2015-2019
University of Padua
2018
Politecnico di Milano
2015-2017
Ospedale Sacro Cuore Don Calabria
2016
YTHDF proteins bind the N6-methyladenosine (m6A)-modified mRNAs, influencing their processing, stability, and translation. Therefore, members of this protein family play crucial roles in gene regulation several physiological pathophysiological conditions. contain a hydrophobic pocket that accommodates m6A embedded RRACH consensus sequence on mRNAs. We exploited presence cage to set up an m6A-competitive assay performed high-throughput screen aimed at identifying ligands binding pocket....
Epitranscriptomic mRNA modifications affect gene expression, with their altered balance detected in various cancers. YTHDF proteins contain the YTH reader domain recognizing m6A mark on and represent valuable drug targets. Crystallographic structures have been determined for all three family members; however, discrepancies are present organization of m6A-binding pocket. Here, we new crystallographic YTHDF1, accompanied by computational studies, showing that this can exist different stable...
The high-throughput docking protocol called ALTA-VS (anchor-based library tailoring approach for virtual screening) was developed in 2005 the efficient silico screening of large libraries compounds by preselection only those molecules that have optimal fragments (anchors) protein target. Here we present an updated version with a broader range potential applications. evaluation binding energy makes use classical force field implicit solvent continuum dielectric approximation. In about 2 days...
Cadherins are a large family of transmembrane calcium-dependent cell adhesion proteins that orchestrate adherens junction formation and crucially involved in tissue morphogenesis. Due to their important role cancer development metastasis, cadherins can be considered attractive targets for drug discovery. A recent crystal structure the complex cadherin extracellular portion small molecule inhibitor allowed identification druggable interface, thus providing viable strategy design dimerization...
Cadherins are transmembrane cell adhesion proteins whose aberrant expression often correlates with cancer development and proliferation. We report the crystal structure of an E-cadherin extracellular fragment in complex a peptidomimetic compound that was previously shown to partially inhibit cadherin homophilic adhesion. The reveals unexpected binding mode allows identification druggable interface, thus paving way future structure-guided design inhibitors against cadherin-expressing solid tumors.
Amadoriases, also known as fructosyl amine oxidases (FAOX), are enzymes that catalyze the de-glycosylation of amino acids. As such, they excellent candidates for development enzyme-based diagnostic and therapeutic tools against age- diabetes-induced protein glycation. However, mostly because lack a complete structural characterization different members family, molecular bases their substrate specificity have yet to be fully understood. The high resolution crystal structures free...
Enzymatic assays based on Fructosyl Amino Acid Oxidases (FAOX) represent a potential, rapid and economical strategy to measure glycated hemoglobin (HbA1c), which is in turn reliable method monitor the insurgence development of diabetes mellitus.
Protein kinase CK2 is an antiapoptotic cancer‐sustaining protein. Curcumin, reported previously as a inhibitor, too bulky to be accommodated in the active site and rapidly degrades solution generating various ATP‐mimetic inhibitors; with detailed comparative analysis, by means of both protein crystallography enzymatic inhibition, ferulic acid was identified principal curcumin degradation product responsible for inhibition. The other derivatives vanillin, feruloylmethane coniferyl aldehyde...
Novel organic‐inorganic polyoxometalates (POMs) decorated with covalent fluorescent tags have been designed for cell internalization. Their localization within model HEK cells is readily accomplished by confocal fluorescence microscopy. While internalization dictated the formation of amphiphilic POM‐based nanostructures, their cytoplasmic‐nuclear trafficking appears to be regulated a subtle interplay domains nanoassemblies which, in turn, impacts dynamic behavior and capability interact membranes.
The vast majority of therapeutic approaches tested so far for prion diseases, transmissible neurodegenerative disorders human and animals, tackled PrPSc , the aggregated infectious isoform cellular protein (PrPC ), with largely unsuccessful results. Conversely, targeting PrPC expression, stability or cell surface localization are poorly explored strategies. We recently characterized mode action chlorpromazine, an anti-psychotic drug known to inhibit replication toxicity by inducing...
Abstract The acetylpyrrole scaffold is an acetylated lysine mimic that has been previously explored to develop bromodomain inhibitors. When tested on the hepatoma cell line Huh7 and breast cancer MDA‐MB‐231, a few compounds in our acetylpyrrole‐thiazole library induced peculiar morphological changes, progressively causing death at increasing concentrations. Their evaluation panel of human bromodomains revealed concurrent inhibition BRPF1 BET bromodomains. To dissect observed cellular...
Cadherins are a large family of calcium-dependent proteins that mediate cellular adherens junction formation and tissue morphogenesis. To date, the most studied cadherins those classified as classical, which further divided into type I or II depending on selected sequence features. Unlike other members classical cadherin family, detailed structural characterization P-cadherin has not yet been fully obtained. Here, high-resolution crystal structure determination closed form human EC1-EC2 is...
Abstract The bromodomain‐containing protein BAZ2A is a validated target in prostate cancer research, whereas the function of its paralogue BAZ2B still undefined. bromodomains and have similar binding site for their natural ligand, acetylated lysine side chain. Here, we present an analysis modes eight compounds belonging to three distinct chemical classes. For all compounds, moiety mimicking ligand engages essentially identical interactions bromodomains. In contrast, rest molecule partially...
BAZ2A is an epigenetic regulator affecting transcription of ribosomal RNA. It overexpressed in aggressive and recurrent prostate cancer, promoting cellular migration. Its bromodomain characterized by a shallow difficult-to-drug pocket. Here, we describe structure-based fragment-growing campaign for the identification ligands bromodomain. By combining docking, competition binding assays, protein crystallography, have extensively explored interactions with rim pocket, particular ionic side...
BAZ2A promotes migration and invasion in prostate cancer. Two chemical probes, the specific BAZ2-ICR, BAZ2/BRD9 cross-reactive GSK2801, interfere with recognition of acetylated lysines histones by bromodomains its BAZ2B paralog. The two probes were tested cancer cell lines opposite androgen susceptibility. BAZ2-ICR GSK2801 showed different cellular efficacies accordance their unequal selectivity profiles. Concurrent inhibition BAZ2 BRD9 did not reproduce effects observed indicating possible...
The bromodomains of BAZ2A and BAZ2B (bromodomain adjacent to zinc finger domain proteins 2) are among the most hard drug 61 human bromodomains. While little is known about role BAZ2B, there strong evidence for opportunity targeting in various cancers. Here, a benzimidazole-triazole fragment that binds acetyl lysine pocket was identified by molecular docking campaign validated competitive binding assays X-ray crystallography. Another ligand observed close proximity soaking experiments using...
Tunable, battery free light emission is demonstrated in a solid state device that compatible with lab on chip technology and easily fabricated via solution processing techniques. A porous one dimensional (1D) photonic crystal (also called Bragg stack or mirror) infiltrated by chemiluminescence (CL) rubrene-based reagents. The mirror has been designed to have the band gap overlapping spectrum of rubrene. CL reaction occurs pores dye modulated according position. This compact, powerless...
The progressive accumulation of Advanced Glycation End-product (AGEs) in the human body leads to several deleterious consequences, involving tissues stiffening and pathologies (aterosclerosis, nephropathy, Alzheimer’s disease). Nowadays there are no effective therapies against AGEs build-up, although a promising strategy is redeglycating enzymes (FAOXs), which however inactive towards entire proteins due their buried active site.