A5025995605- Chemical Synthesis and Analysis
- Cell Adhesion Molecules Research
- Carbohydrate Chemistry and Synthesis
- Synthetic Organic Chemistry Methods
- Glycosylation and Glycoproteins Research
- Cell death mechanisms and regulation
- Asymmetric Synthesis and Catalysis
- Monoclonal and Polyclonal Antibodies Research
- RNA Interference and Gene Delivery
- Microbial Natural Products and Biosynthesis
- Nanoparticle-Based Drug Delivery
- Chemical Synthesis and Reactions
- Click Chemistry and Applications
- Synthesis of heterocyclic compounds
- Radical Photochemical Reactions
- Fluorine in Organic Chemistry
- ATP Synthase and ATPases Research
- Immune Response and Inflammation
- Synthesis and Catalytic Reactions
- Catalytic C–H Functionalization Methods
- Neuropeptides and Animal Physiology
- Cyclopropane Reaction Mechanisms
- RNA and protein synthesis mechanisms
- Sulfur-Based Synthesis Techniques
- Protease and Inhibitor Mechanisms
Institute of Molecular Science and Technologies
2009-2020
Mylan (Switzerland)
2015-2016
Milano University Press
2016
Consorzio Roma Ricerche
2014-2016
University of Milan
1999-2012
National Research Council
1998-2012
National Academies of Sciences, Engineering, and Medicine
2011
Sigma Tau (Italy)
2001
GTx (United States)
2000
University of Konstanz
1996-1999
Integrin αvβ3 is an adhesion molecule involved in physiological and pathological angiogenesis as well tumor invasion metastasis. Therefore, it considered important target for molecular imaging delivery of therapeutics cancer, there a strong interest developing novel agents interacting with this protein. Nevertheless, the interaction individual ligands often still weak efficient targeting, many research groups have synthesized multivalent displays order to overcome problem. Gold nanoparticles...
The Human antigen R protein (HuR) is an RNA-binding that recognizes U/AU-rich elements in diverse RNAs through two RNA-recognition motifs, RRM1 and RRM2, post-transcriptionally regulates the fate of target RNAs. natural product dihydrotanshinone-I (DHTS) prevents association HuR vitro cultured cells by interfering with binding to RNA. Here, we report structural determinants interaction between DHTS impact on mRNAs transcriptome-wide. NMR titration Molecular Dynamics simulation identified...
Amyotrophic Lateral Sclerosis (ALS) is a fatal disease characterized by the degeneration of upper and lower motor neurons (MNs). We find significant reduction retromer complex subunit VPS35 in iPSCs-derived MNs from ALS patients, post mortem explants SOD1G93A mice. Being involved trafficking hydrolases, pathological hallmark ALS, we design, synthesize characterize an array stabilizers based on bis-guanylhydrazones connected 1,3-phenyl ring linker. select compound 2a as potent bioavailable...
XIAP (X-linked inhibitor of apoptosis protein) is an anti-apoptotic protein exerting its activity by binding and suppressing caspases. As overexpressed in several tumours, which it apparently contributes to chemoresistance, because vivo antagonised second mitochondria-derived activator caspase (SMAC)/direct apoptosis-binding with low pI, small molecules mimicking SMAC (so called SMAC-mimetics) can potentially overcome tumour resistance promoting apoptosis. Three homodimeric compounds were...
Abstract We report the synthesis of novel chelates Gd and 68 Ga with DPTA, DOTA, HP‐DOA3, as well AAZTA, a chelating agent developed by our research group. These agents were appropriately conjugated, prior to metal complexation, DB58, an RGD peptidomimetic, conformationally constrained on azabicycloalkane scaffold endowed high affinity for integrin α ν β 3 . Because is involved in neo‐angiogenesis solid tumors also directly expressed cancer cells (e.g. glioblastomas, melanomas) ovarian,...
The human antigen R (HuR) is an RNA-binding protein known to modulate the expression of target mRNA coding for proteins involved in inflammation, tumorigenesis, and stress responses a valuable drug target. We previously found that dihydrotanshinone-I (DHTS, 1) prevents association HuR with its RNA substrate, thus imparing function. Herein, inspired by DHTS structure, we designed synthesized array ortho-quinones (tanshinone mimics) using function-oriented synthetic approach. Among others,...
Abstract The aim of the present study was to identify specific αvβ3/αvβ5 integrin antagonists active on tumor-induced angiogenesis. To this purpose, in vitro integrin-binding assays were used screen a library conformationally constrained bicyclic lactam Arg-Gly-Asp–containing pseudopeptides. results identified ST1646 as high-affinity ligand for αvβ3 and αvβ5 integrins with negligible interacting α5β1 integrin. In all assays, equipotent or more potent than well-characterized c(RGDfV)...
A perfect fit: The nanomolar affinity of a diketopiperazine-derived cyclic RGD-peptidomimetic for the integrin αvβ3 receptor can be attributed to its high structural pre-organization. trans-diketopiperazine scaffold induces an extended RGD disposition permitting all important interactions with extracellular domain integrin. metal ion in metal-ion-dependent adhesion site region is represented by magenta sphere. Detailed facts importance specialist readers are published as "Supporting...
[structure: see text]. A small library of cyclic RGD pseudopentapeptides incorporating stereoisomeric 6,5- and 7,5-fused bicyclic lactams was synthesized with the aim developing active selective integrin antagonists. The solid-phase synthesis activity these derivatives is described. approach led to two most known inhibitors alpha(V)beta3 receptor.
Cyclic RGD-containing functionalized azabicycloalkane peptides were synthesized with the aim of developing high-affinity selective integrin ligands as carriers for therapeutic and diagnostic purposes. Herein we describe synthesis in vitro screening these RGD derivatives, well determination their conformational properties solution by spectroscopic computational methods. Docking studies X-ray crystal structure extracellular domain alpha(v)beta(3) also performed to elucidate structural binding...
The efficacy of taxane-based antitumor therapy is limited by several drawbacks which result in a poor therapeutic index. Thus, the development approaches that favor selective delivery taxane drugs (e.g., paclitaxel, PTX) to disease area represents truly challenging goal. On basis strategic role integrins tumor cell survival and progression, as well on integrin expression tumors, novel molecular conjugates were prepared where PTX covalently attached either cyclic AbaRGD (Azabicycloalkane-RGD)...
α V β 3 Integrins are a widely recognized target for in vivo molecular imaging of pathological conditions such as inflammation, cancer and rheumatoid arthritis. We have evaluated the sensitivity new, near‐infrared fluorescence (NIRF), RGD cyclic probe (DA364) noninvasive detection integrin‐overexpressing tumors. DA364's binding affinity integrin was first vitro . Human integrin‐positive, U‐87 MG glioblastoma cells were then xenografted nude mice, DA364 injected intravenously (i.v.) to...
Novel liposemipeptides hanging cyclic azabicycloalkane-RGD or aminoproline-RGD terminals were synthesized and incorporated into liposomal nanoparticles cAba/cAmpRGD-LNP5 3C/3D. Liposomes with similar composition lacking semipeptide conjugates constructed for comparison (LNP, 3A), physical encapsulation of the anticancer doxorubicin drug in both targeted untargeted liposomes was accomplished. Microstructural analysis performed by dynamic light scattering (DLS), small-angle neutron (SANS),...
A fluorous silyl ether tag as protecting group at the anomeric position of sugar acceptors allows rapid synthesis oligosaccharides by reducing purification procedures to a simple and fast solid-phase extraction.