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D'Amelio N.,Bracco Imaging SpA CRB Trieste | D'Amelio N.,CBM S.r.l. Consorzio per Il Centro di Biomedicina Molecolare | D'Amelio N.,University College London | Esteban C.,National University of San Luis | And 8 more authors.
Journal of Physical Chemistry B | Year: 2013

Chitlac is a biocompatible modified polysaccharide composed of a chitosan backbone to which lactitol moieties have been chemically inserted via a reductive N-alkylation reaction with lactose. The physical-chemical and biological properties of Chitlac that have been already reported in the literature suggest a high accessibility of terminal galactose in the lactitol side chain. This finding may account for its biocompatibility which makes it extremely interesting for the production of biomaterials. The average structure and the dynamics of the side chains of Chitlac have been studied by means of NMR (nuclear Overhauser effect and nuclear relaxation) and molecular dynamics to ascertain this hypothesis. A complete assignment of the 1H and 13C NMR signals of the modified polysaccharide has been accomplished together with the determination of the apparent pKa values of the primary and secondary amines (6.69 and 5.87, respectively). NMR and MD indicated a high mobility of Chitlac side chains with comparable average internuclear distances between the two techniques. It was found that the highly flexible lactitol side chain in Chitlac can adopt two distinct conformations differing in the orientation with respect to the polysaccharide chain: a folded conformation, with the galactose ring parallel to the main chain, and an extended conformation, where the lactitol points away from the chitosan backbone. In both cases, the side chain resulted to be highly hydrated and fully immersed in the solvent. © 2013 American Chemical Society.

D'Amelio N.,Bracco Imaging SpA CRB Trieste | D'Amelio N.,CBM S.r.l. Consorzio per Il Centro di Biomedicina Molecolare | Coslovi A.,University of Trieste | Coslovi A.,Novartis | And 3 more authors.
Carbohydrate Research | Year: 2012

The present work aims at understanding the structural basis of the biological recognition of Tn antigen (GalNAc-α-O-l-Ser), a specific epitope expressed by tumor cells, and the role of its amino acidic moiety in the interaction with its receptor (the isolectin B4 extracted from Vicia villosa). An NMR structural characterization of the α and β anomers, based on J couplings and molecular modeling revealed a structure in very good agreement with data reported in literature for variants of the same molecules. In order to demonstrate the involvement of the amino acid in the ligand-receptor recognition, also GalNAc-α-O-d-Ser was studied; the change in the stereochemistry is in fact expected to impact on the interaction only in case the serine is part of the epitope. Relaxation properties in the presence of the receptor clearly indicated a selective recognition of the natural l form, probably due to the formation of a water-mediated hydrogen bond with Asn 129 of the protein. © 2012 Elsevier Ltd. All rights reserved.

Fontanive L.,University of Trieste | D'Amelio N.,Bracco Imaging SpA CRB Trieste | D'Amelio N.,IMDEA Madrid Institute for Advanced Studies | Cesaro A.,University of Trieste | And 8 more authors.
Molecular Pharmaceutics | Year: 2015

The present work reports a thorough conformational analysis of iodinated contrast media: iomeprol, iopamidol (the world"s most utilized contrast agent), and iopromide. Its main aim is the understanding of the complex structural features of these atropisomeric molecules, characterized by the presence of many conformers with hindered rotations, and of the role of atropisomerism in the physicochemical properties of their aqueous solutions. The problem was tackled by using an extensive analysis of 13C NMR data on the solutions of whole molecules and of simple precursors in addition to FT-IR investigation and molecular simulations. This analysis demonstrated that out of the many possible atropisomers, only a few are significantly populated, and their relative population is provided. The conformational analysis also indicated that the presence of a sterically hindered amidic bond, allowing a significant population of cis forms (E in iopromide and exo in iomeprol), may be the basis for an increased thermodynamic solubility of concentrated solutions of iomeprol. © 2015 American Chemical Society.

Pellis A.,University of Trieste | Corici L.,SPRIN S.p.a. C o BIC Incubatori FVG | Sinigoi L.,University of Trieste | Sinigoi L.,SPRIN S.p.a. C o BIC Incubatori FVG | And 5 more authors.
Green Chemistry | Year: 2015

There is an enormous potential for synthesizing novel bio-based functionalized polyesters under environmentally benign conditions by exploiting the catalytic efficiency and selectivity of enzymes. Despite the wide number of studies addressing in vitro enzymatic polycondensation, insufficient progress has been documented in the last two decades towards the preparative and industrial application of this methodology. The present study analyses bottlenecks hampering the practical applicability of enzymatic polycondensation that have been most often neglected in the past, with a specific focus on solvent-free processes. Data here presented elucidate how classical approaches for enzyme immobilization combined with batch reactor configuration translate into insufficient mass transfer as well as limited recyclability of the biocatalyst. In order to overcome such bottlenecks, the present study proposes thin-film processes employing robust covalently immobilized lipases. The strategy was validated experimentally by carrying out the solvent-free polycondensation of esters of adipic and itaconic acids. The results open new perspectives for enlarging the applicability of biocatalysts in other viscous and solvent-free syntheses. This journal is © The Royal Society of Chemistry 2015.

D'Amelio N.,Bracco Imaging SpA CRB Trieste | D'Amelio N.,CBM S.r.l. Consorzio per Il Centro di Biomedicina Molecolare | D'Amelio N.,CSIC - National Center for Metallurgical Research | Aroulmoji V.,Advanced Research Center for Health | And 3 more authors.
Journal of Molecular Structure | Year: 2012

Irinotecan is an antitumor drug mostly used in the treatment of colorectal cancer. Its efficacy is influenced by the chemical state of the molecule undergoing chemical equilibria, metabolic changes and photodegradation. In this work, we describe the chemical equilibria of the drug in dimethyl sulfoxide (DMSO). The energetic barrier for hindered rotation around the bond connecting the piperidino - piperidino moiety with the camptothecin-like fragment was evaluated. Furthermore, we showed how the molecule aggregates in DMSO solution forming dimeric species able to prevent its degradation. The equilibrium constant for self-aggregation was determined by NMR based on the assumption of the isodesmic model. The formation of a dimer was highlighted by NMR diffusion ordered spectroscopy (NMR-DOSY) experiments at the concentrations used. Structural features of the complex were inferred by NOE and 13C chemical shift data. Molecular modelling of the complex driven by experimental data, lead to a structure implying the formation of two hydrogen bonds involving the lactone ring whose opening is one of the main causes of drug degradation. This species is probably responsible for the improved stability of the drug at concentrations higher than 1 mM. © 2012 Elsevier B.V. All rights reserved.

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