on Chemistry (Weinheim an der Bergstrasse, Germany)
by Coppola C, Paciello A, Mangiapia G, Licen S, Boccalon M, De Napoli L, Paduano L, Tecilla P, Montesarchio D
A novel fluorescently labelled synthetic ionophore, based on a cyclic phosphate-linked disaccharide (CyPLOS) backbone and decorated with four tetraethylene glycol tails carrying dansyl units, has been synthesised in 12 steps in 26% overall yield. The key intermediate in the synthetic strategy is a novel glucoside building block, serving through its 2- and 3-hydroxy groups as the anchor point for flexible tetraethylene glycol tentacles with reactive azido moieties at their ends. To test the versatility of this glucoside scaffold, it was preliminarily functionalised with a set of diverse probes--as fluorescent, redox-active or hydrophobic tags--either by reduction of the azides followed by condensation with activated carboxylic acid derivatives, or by a direct coupling with a terminal alkyne in a Cu(I)-promoted 1,3-dipolar cycloaddition. Tagging of the monomeric building block with dansyl residues allowed us to prepare a fluorescent, amphiphilic macrocycle, which was investigated for its propensity to self-aggregate in CDCl(3)--studied by means of concentration-dependent (31)P NMR spectroscopy experiments--and in aqueous solution, in which combined dynamic light scattering (DLS) and small-angle neutron scattering (SANS) measurements provided a detailed physico-chemical analysis of the self-assembled systems, mainly organised in the form of large vesicles. Its ion-transport properties through phospholipid bilayers, determined by HPTS fluorescence assays, showed this compound to be more active than the previously synthesised CyPLOS congeners. Solvent-dependent fluorescence changes for the labelled ionophore in liposome suspension established that the dansyl moieties are dispersed in environments with polarity intermediate between those of CH(2)Cl(2) and propan-2-ol, suggesting that the CyPLOS tentacles infiltrate the mid-polar region of the membranes.
on Journal of cardiovascular medicine (Hagerstown, Md.)
by Maurea N, Coppola C, Ragone G, Frasci G, Bonelli A, Romano C, Iaffaioli RV
In many cases, early-stage breast cancer is now curable, and metastatic disease can be chronic consequent to the advent of new therapeutic tools. Unfortunately, some treatments have been associated with adverse cardiovascular effects. Indeed, in many breast cancer survivors, the risk of cardiovascular disease is higher than the risk of cancer recurrence. The clinical challenge of preventing cardiovascular complications in patients undergoing antineoplastic treatment has two aims, more effective life-saving treatment of patients, and prevention of morbidity and cardiovascular mortality in the short term and long term. The aim of the present study is to review the rapidly evolving therapeutic strategies designed to treat early-stage breast cancer. The review highlights the need for more data on the impact of new biological drugs (targeted therapy) on the cardiovascular apparatus. Finally, given the complexity of targeted and other novel treatments, cancer patients are best managed through a multidisciplinary approach.
on Organic & biomolecular chemistry
by Licen S, Coppola C, D'Onofrio J, Montesarchio D, Tecilla P
The ion transport properties of a new family of synthetic ionophores based on cyclic phosphate-linked oligosaccharide (CyPLOS) macrocycles are described.
on Journal of neurology, neurosurgery, and psychiatry
by Mauro C, Giaccone G, Piscosquito G, Lavorgna A, Nigro M, Di Fede G, Leonardi A, Coppola C, Formisano S, Tagliavini F, Cotrufo R, Puoti G
A young man, presenting with early onset of personality and behavioural changes followed by slowly progressive cognitive impairment associated with marked bi-parietal cerebral atrophy, was found to carry a novel seven extra-repeat insertional mutation in the prion protein gene (PRNP). In vitro, the mutated recombinant prion protein (PrP) showed biochemical properties that were consistent with pathological PrP variants. Our results further underline the heterogeneity of neurological pictures associated with insertional mutations of PRNP, indicating the diagnostic difficulties of sporadic cases with early-onset atypical dementia.
on Nucleic acids symposium series (2004)
by Coppola C, D'Onofrio J, Di Fabio G, De Napoli L, Montesarchio D
We here describe the synthesis of a series of novel bicyclic ribonucleoside derivatives, with 18-crown-6 ether moieties attached via their ribose 2- and 3- positions, as first examples of crown ether ring-fused nucleosides, to be evaluated as antiviral and/or antitumoral agents.
on Nucleic acids symposium series (2004)
by Di Fabio G, Coppola C, D'Onofrio J, De Napoli L, Montesarchio D
A versatile approach to develop libraries of diverse 5',3'-bis-conjugated oligonucleotides (ODNs) is here described. The usage of ad hoc derivatized solid supports, to which the first nucleoside unit is attached through a phosphate linkage, opens easy synthetic access to a large variety of hybrid bis-conjugated oligomers. The G-quadruplex forming d((5')TGGGAG(3')) sequence, as a potential anti-HIV agent, has been here used as a model system.
on The Journal of organic chemistry
by Coppola C, Saggiomo V, Di Fabio G, De Napoli L, Montesarchio D
Novel amphiphilic cyclic disaccharide analogues, in which the saccharide units are connected through stable phosphodiester linkages (CyPLOS, Cyclic Phosphate-Linked OligoSaccharides) and decorated with long lipophilic tentacles at the 2- and 3-OH moieties, have been synthesized. Their propensity to self-aggregation has been investigated by means of 1H and 31P NMR experiments, making it possible to determine for these macrocycles critical aggregation concentration values in the millimolar range.
on Anticancer research
by Giorgio A, De Stefano G, Coppola C, Ferraioli G, Esposito V, Di Sarno A, Giorgio V, De Stefano M, Sangiovanni V, Liorre G, Del Viscovo L
To evaluate the role of low mechanical index (MI) contrast-enhanced sonography (CEUS) for the characterization of small hepatocellular carcinomas (HCC) in cirrhotic patients by comparing the results to ultrafast dynamic gadolinium-enhanced magnetic resonance imaging (MRI) studies.