A5089347292- Cell Adhesion Molecules Research
- Cancer-related gene regulation
- Receptor Mechanisms and Signaling
- Immune Response and Inflammation
- Computational Drug Discovery Methods
- Chemical Synthesis and Analysis
- Neuropeptides and Animal Physiology
- Peptidase Inhibition and Analysis
- Epigenetics and DNA Methylation
- Advanced Chemical Physics Studies
- Monoclonal and Polyclonal Antibodies Research
- Chemokine receptors and signaling
- Protein Structure and Dynamics
- Sulfur Compounds in Biology
- Signaling Pathways in Disease
- Ubiquitin and proteasome pathways
- Biochemical and Structural Characterization
- Ion Transport and Channel Regulation
- Protein Kinase Regulation and GTPase Signaling
- Genomics and Chromatin Dynamics
- Advanced Biosensing Techniques and Applications
- Protein Degradation and Inhibitors
- S100 Proteins and Annexins
- RNA and protein synthesis mechanisms
- Machine Learning in Materials Science
IRCCS Ospedale San Raffaele
2015-2024
Vita-Salute San Raffaele University
2016-2019
Istituti di Ricovero e Cura a Carattere Scientifico
2016-2019
Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele
2017-2019
Mylan (Switzerland)
2018-2019
San Raffaele University of Rome
2018
Dulbecco Telethon Institute
2010-2013
University of Milan
2005-2008
Abstract Chemokine heterodimers activate or dampen their cognate receptors during inflammation. The CXCL12 chemokine forms with the fully reduced (fr) alarmin HMGB1 a physiologically relevant heterocomplex (frHMGB1•CXCL12) that synergically promotes inflammatory response elicited by G-protein coupled receptor CXCR4. molecular details of complex formation were still elusive. Here we show an integrated structural approach frHMGB1•CXCL12 is fuzzy heterocomplex. Unlike previous assumptions,...
Metabolomics, similarly to other high-throughput "-omics" techniques, generates large arrays of data, whose analysis and interpretation can be difficult not always straightforward. Several software for the detailed metabolomics statistical are available, however there is a lack simple protocols guiding user through standard data. Herein we present "muma", an R package providing step-wise pipeline univariate multivariate analyses. Based on published algorithms muma provides user-friendly...
An NRP1-independent, non-natural SEMA3A mutant isoform is a parenterally deliverable anticancer drug that normalizes the vasculature.
A two-step posttranslational modification of AQP8 provides a mechanism regulating plasma membrane H 2 O conductance.
Ain't got that swing(-out): The cyclopeptide isoDGR is emerging as a new αvβ3 integrin binding motif. Agreement between the results of computational and biochemical studies reveals isoDGR-containing cyclopeptides are true antagonists block in its inactive conformation (see scheme). isoDGR-based ligands may give without paradoxical effects. Detailed facts importance to specialist readers published "Supporting Information". Such documents peer-reviewed, but not copy-edited or typeset. They...
Cell mates: Various ligand–receptor interactions in different human cancer cell lines were probed directly by two-dimensional transferred-NOE spectroscopy (see picture) to prove recognition specificity and determine an affinity ranking of several ligands. Detailed facts importance specialist readers are published as "Supporting Information". Such documents peer-reviewed, but not copy-edited or typeset. They made available submitted the authors. Please note: The publisher is responsible for...
A pretty pair: Metadynamics/docking proved itself as an innovative technique combination to improve the rational design of diagnostic and therapeutic agents based on isoDGR motif (see picture; FES=free-energy surface). The coupling these techniques might be exploited for other ligand–receptor systems following identification appropriate collective variables characterization ligand conformational ensembles. Detailed facts importance specialist readers are published "Supporting Information"....
Abstract Hemojuvelin ( HJV ), the coreceptor of BMP ‐ SMAD pathway that up‐regulates hepcidin transcription, is a repulsive guidance molecule RGM c) which undergoes complex intracellular processing. Following autoproteolysis, it exported to cell surface both as full‐length and heterodimeric protein. In vitro membrane (m‐ ) cleaved by transmembrane serine protease TMPRSS 6 attenuate signalling inhibit expression. this study, we investigated number position cleavage sites mutagenizing arginine...
NGR (asparagine-glycine-arginine) is a tumor vasculature-homing peptide motif widely used for the functionalization of drugs, nanomaterials and imaging compounds cancer treatment diagnosis. Unfortunately, this has strong propensity to undergo rapid deamidation. This reaction, which converts into isoDGR, associated with receptor switching from CD13 integrins, potentially important manufacturing, pharmacological toxicological implications. It found that glycine N-methylation NGR-tagged...
The isoDGR sequence is an integrin-binding motif that has been successfully employed as a tumor-vasculature-homing molecule or for the targeted delivery of drugs and diagnostic agents to tumors. In this context, we previously demonstrated cyclopeptide 2, product conjugation c(CGisoDGRG) (1) 4-(N-maleimidomethyl)cyclohexane-1-carboxamide, can be used tumor-homing ligand nanodrug neoplastic tissues. Here, combining NMR, computational, biochemical methods, show succinimide ring contained in 2...
Abstract Aminopeptidase N/CD13, a membrane-bound enzyme upregulated in tumor vasculature and involved angiogenesis, can be used as receptor for the targeted delivery of drugs to tumors through ligand-directed targeting approaches. We describe novel peptide ligand (VGCARRYCS, called “G4”) that recognizes CD13 with high affinity selectivity. Enzymological computational studies showed G4 is competitive inhibitor binds catalytic pocket its N-terminal region. Fusing C-terminus necrosis...
We combined metadynamics, docking and molecular mechanics/generalised born surface area (MM/GBSA) re-scoring methods to investigate the impact of single multiple N-methylation on a set RGD cyclopeptides displaying different affinity for integrin αIIbβ3. rationalised conformational effects induced by its interplay with receptor affinity, obtaining good agreement experimental data. This approach can be exploited before entering time-consuming expensive synthesis binding experiments.
We have uncovered that long-term circulation of seasonal influenza A viruses (IAV) in the human population resulted progressive acquisition increased sensitivity to a component innate immune response: type I interferon-inducible TRIM22 protein, which acts as restriction factor by inducing polyubiquitination IAV nucleoprotein (NP). show four arginine residues present NP 1918 H1N1 pandemic strain and early postpandemic strains were progressively substituted for lysines between 2009, rendering...
Sotos syndrome is an overgrowth caused by mutations within the functional domains of NSD1 gene coding for NSD1, a multidomain protein regulating chromatin structure and expression. In particular, PHDVC5HCHNSD1 tandem domain, composed classical (PHDV) atypical (C5HCH) plant homeo-domain (PHD) finger, target several pathological missense-mutations. also crucial NSD1-dependent transcriptional regulation interacts with C2HR domain repressor Nizp1 (C2HRNizp1) in vitro. To get molecular insights...
Human Sp140 protein is a leukocyte-specific member of the speckled (Sp) family (Sp100, Sp110, Sp140, Sp140L), class multi-domain nuclear proteins involved in intrinsic immunity and transcriptional regulation. regulates macrophage program implicated several haematologic malignancies. Little known about structural domains its post-translational modifications. We used mass spectrometry biochemical experiments to investigate endogenous SUMOylation Burkitt's Lymphoma cells sites HEK293T cells,...
A critical assessment of the reproducibility NMR parameters β amino acids pinpoints major weaknesses eight widely used force fields in reproducing equilibrium conformational properties highly constrained cyclic peptides containing isoAspartic acid.
Eine gelungene Kombination: Ein gekoppeltes Metadynamik-/Docking-Verfahren erweist sich als exzellente Technik für den gezielten Entwurf von diagnostischen und therapeutischen Wirkstoffen basierend auf dem isoDGR-Motiv (siehe Bild; FES=Hyperfläche der freien Energie). Das Verfahren könnte auch andere Ligand-Rezeptor-Systeme genutzt werden.
Combining 2D STD-NMR, computation, biochemical assays and click-chemistry, we have identified a chromogranin-A derived compound (5) that has high affinity bi-selectivity for αvβ6 αvβ8 integrins is stable in microsomal preparations. 5 suitable nanoparticle functionalization delivery to cancer cells, holding promise diagnostic and/or therapeutic applications.
Graphical abstractAbstractPHD fingers are small chromatin binding domains, that alone or in tandem work as versatile interaction platforms for diversified activities, ranging from the decoding of modification status histone tails to specific recognition non-histone proteins. They play a crucial role their host protein mutations thereof cause several human malignancies. Thus, PHD starting be considered valuable pharmacological targets. While inhibitors chemical probes activity emerging,...
Wer ist der beste? Verschiedene Ligand-Rezeptor-Wechselwirkungen in humanen Krebszelllinien wurden direkt mithilfe zweidimensionalen TR-NOE-Spektroskopie untersucht (siehe Bild), um die Spezifität molekularen Erkennung zu prüfen und ein Affinitäts-Ranking mehrerer Liganden erhalten.