126,202 research outputs found
Non trivial chiroptical responses: experimental and theoretical investigations
No full textIn the past few years, our two groups of research have been collaborating on a number of projects
dealing with the assignment of the absolute configuration (AC) of complex chiral molecules of phar-
macological interest in the disordered phase. [1] These studies have been mainly carried out by means of
electronic circular dichroism (ECD) spectroscopy and quantum mechanical (QM) calculations at the den-
sity functional theory (DFT) level of approximation. Particular attention has been payed to non-trivial
chiroptical responses due to conformational flexibility and solvation.
Beside these shared activities, some more specific research fields have been investigated too. In par-
ticular, the Bologna group has performed studies concerning the hyphenation of enantioselective HPLC
methods with detection systems based on ECD [2] and the characterization of biomolecular recognition
phenomena between drugs and target or carrier macromolecules. [3] The Salerno group has developed
some skills in vibrational circular dichroism (VCD) [4] and chiral NMR [5] spectroscopies, thanks to the
availability of a VCD spectrometer and previous studies concerning the non-linear response of molecules
exposed to radiation.
[1] (a) C. Bertucci, M. Pistolozzi, D. Tedesco, R. Zanasi, R. Ruzziconi, A. M. Di Pietra, J. Chromatogr. A 2012, 1232,
128–133; (b) D. Tedesco, R. Zanasi, A. Guerrini, C. Bertucci, Chirality 2012, 24, 741–750; (c) F. Dong, J. Li, B.
Chankvetadze, Y. Cheng, J. Xu, X. Liu, Y. Li, X. Chen, C. Bertucci, D. Tedesco, R. Zanasi, Y. Zheng, Environ. Sci.
Technol. 2013, 47, 3386–3394; (d) W. J. Andrioli, R. Conti, M. J. Araújo, R. Zanasi, B. C. Cavalcanti, V. Manfrim,
J. S. Toledo, D. Tedesco, M. O. de Moraes, C. Pessoa, A. K. Cruz, C. Bertucci, J. Sabino, D. N. P. Nanayakkara,
M. T. Pupo, J. K. Bastos, J. Nat. Prod. 2014, 77, 70–78; (e) D. Tedesco, R. Zanasi, I. W. Wainer, C. Bertucci, J.
Pharm. Biomed. Anal. 2014, 91, 92–96.
[2] (a) C. Bertucci, D. Tedesco, J. Chromatogr. A 2012, 1269, 69–81; (b) D. Tedesco, A. M. Di Pietra, F. Rossi, M.
Garagnani, E. Del Borrello, C. Bertucci, V. Andrisano, J. Pharm. Biomed. Anal. 2013, 81-82, 76–79.
[3] (a) G. A. Ascoli, E. Domenici, C. Bertucci, Chirality 2006, 18, 667–679; (b) M. Pistolozzi, C. Bertucci, Chirality
2008, 20, 552–558;
[4] (a) A. Lattanzi, A. Russo, P. Rizzo, G. Monaco, R. Zanasi, Chirality 2010, 22, E130–E135; (b) A. Massa, P. Rizzo,
G. Monaco, R. Zanasi, Tetrahed. Lett. 2013, 54, 6242–6246.
[5] (a) S. Pelloni, P. Lazzeretti, R. Zanasi, J. Chem. Theory Comput. 2007, 3, 1691–1698; (b) G. Monaco, R. Zanasi,
Chirality 2011, 23, 752–755
Search For the Decays B-d(0)-]gamma-gamma and B-s(0)-]gamma-gamma
No full textA search for the decays B-d,s(0) --> gamma gamma in 2.95 million hadronic Z decays has been performed using the L3 detector at LEP. No candidates are found in the signal region and upper limits have been set on the branching ratios: Br(B-d(0) --> gamma gamma) gamma gamma) < 14.8 x 10(-5) at 90% CL. These are the first limits set on these exclusive rare decays
Measurement of the Lifetime of B-hadrons and A Determination of [vcb]
No full textFrom a fit to the impact parameter distribution of lepton tracks from semileptonic b decay, the lifetime of B-hadrons produced in e+e- collisions at the Z0 is measured to be 1.32 +/- 0.08 (stat.) +/- 0.09 (syst.) ps. Combined with an earlier measurement of the branching ratio Br(B --> lvX), the CKM matrix element \V(cb)\ is determined to be 0.046 +/- 0.002 (exp.) -0.003(+0.004) (theory)
Measurement of the Weak Charged Current Structure In Semileptonic B-hadron Decays At the Z-peak
No full textThe neutrino energy spectrum in semileptonic b-hadron decays with identified energetic electrons and muons has been measured. The observed relative energy sharing between the neutrino and the charged lepton is found to be well described with a W-+/- polarization obtained from a free b-quark decay model with a (V-A)x(V-A) decay structure. The alternative of a (V+A) x(V-A) decay structure is excluded with a significance of more than 6 standard deviations. The possibility that hadronic corrections to the b-hadron decay destroy any W-+/- polarization is disfavored by more than 3 standard deviations
BIORECOGNITION STUDIES: MULTIMETHODOLOGICAL APPROACH
No full textMolecular recognition phenomena play crucial roles in a number of biological processes. Thus the elucidation of these processes deserves the understanding of the basic forces that determine the involved protein-protein or small molecule-protein interactions. This aim determines a growing need of methodologies for studying any specific biomolecular event as well as the structural elements that drive the process. In order to determine the equilibrium and/or kinetic constants for binding, these techniques must factor the concentrations of free probe and target molecules, as well as of the corresponding complex. Many methodologies are well suited to get information on the complex formation as well as on the funzionalizing high structures. However a multimethodological approach is often essential to give a deeper insight in the understanding of the recognition process, taking advantage of the peculiarity of each methodology.
Here we report the use of biochromatography, circular dichroism, and optical biosensors in key activities in drug discovery and developments, e.g. identification of protein function modulators, and early determination of ADME parameters. In particular, applications of the different methodologies will be presented for determining the distribution parameters of anticancer and antiviral drugs, studying the drug binding to target proteins, and getting information on the association of functional proteins into homo and hetero-oligomers (1-4). As far as the distribution parameters determination is concerned, the binding of drugs to albumins from different species have been characterized in terms of bound fraction, affinity constant, binding area localization, and stereochemistry of the drug-protein complex. The relevance of target discovery and validation will be then addressed by applying optical biosensor technique and circular dichroism spectroscopy to anticancer drugs. Finally, the characterization of the molecular interactions between herpes simplex virus (HSV) cellular receptors and glycoproteins showing receptor-binding activity will be reported. The use of different methodologies resulted of great relevance for understanding the glycoprotein-mediated interference to infection and then to get information on the mechanism involved in the virus entry.
1. S. Cimitan, M.T. Lindgren, C. Bertucci, U.H. Danielson
J.Med.Chem., 2005, 48:7282-9.
2. T. Gianni, A. Piccoli, C. Bertucci, G. Campadelli-Fiume. J Virol., 2006, 80:2216-24.
3. G.A. Ascoli, E. Domenici, C. Bertucci, Chirality, 2006, 18:667-79.
4. B. Sanavio, A. Piccoli, T. Gianni, C. Bertucci, BBA-PRO, 2007, in press
The AMS experiment: Results and perspectives
No full textThe Alpha Magnetic Spectrometer (AMS) experiment operates since May 2011 on board of the International Space Station to search for primordial antimatter, to study the light anti-matter components in the Cosmic Rays (CR) and to perform a precision study of the CR composition and energy spectrum. More than 60 billion events have been collected by the instrument up to now thanks to its large acceptance and the long exposure time. In this contribution we will discuss the most recent results, reviewing the instrument design and performances as well as the data analysis procedures enabling their achievement
FLUORESCENCE BASED STUDIES ON BETA-AMYLOID MISFOLDING AND AGGREGATION
No full textRecent findings about the relationship between amyloid b-peptide (Ab) accumulation and cognitive decline in Alzheimer's disease (AD) suggest a complex role for Ab in this neurodegenerative process. The transition of Ab soluble monomers to toxic small oligomers involves an initial transition from a non organized/a-helix monomer to a b-sheet rich conformer. This early step represents a suitable target to design new potent inhibitors and obtain effective therapeutics for AD. Moreover, several chaperone molecules are though to accelerate amyloid aggregation, i.e., the enzyme acetylcholinesterase (AChE). Since most of the marketed drugs for AD are AChE inhibitors, the investigation of the inhibitory potency against the AChE-induced amyloid aggregation exerted by anti-cholinesterase agents definitively represents an interesting area of investigation for drug discovery. The in vitro Ab aggregation can be evaluated by a fluorescence-based assay by using Thioflavin T (ThT) as fluorescent dye. More in details, ThT specifically binds to amyloid fibrils (in the beta-sheet conformation) giving rise to an intense specific emission band (lem = 490 nm) in its fluorescent spectrum (1-3). Therefore the increase in the specific fluorescence emission was used to monitor amyloid fibrils formation. Two fluorescence-based assays specifically developed (4,5) for the evaluation of beta-amyloid self- and AChE-induced aggregation were applied to follow the aggregation process as well as to screen for potential inhibitors. The concomitant use of circular dichroism spectroscopy was helpful to set up the optimal experimental conditions and to draw some hypotheses on the mechanism of action of known and new inhibitors.
(1) H. Naiki, K. Higuchi, K. Nakakuki, T. Takeda, Lab. Invest. 1991, 65, 104.
(2) H. LeVine, Protein Sci. 1993, 2, 404.
(3) H. LeVine 3rd, Methods Enzymol. 1999, 309, 274.
(4) M. Bartolini, C. Bertucci, M.L. Bolognesi, A. Cavalli, C. Melchiorre, V. Andrisano, Chembiochem 2007, 8, 2152.
(5) M. Bartolini, C. Bertucci, V. Cavrini, V. Andrisano, Biochem. Pharmacol. 2003, 65, 407
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Tests Qed At Lep Energies Using E(+)e(-)-]gamma-gamma(gamma) and E(+)e(-)-]l(+)l(-)gamma-gamma
No full textTotal and differential cross sections for the process e(+)e(-) --> gamma gamma(gamma), and the total cross section for the process e(+)e(-) --> gamma gamma gamma, are measured at energies around 91 GeV using the data collected with the L3 detector from 1991 to 1993. We set lower limits, at 95% CL, on a contact interaction energy scale parameter Lambda > 602 GeV, on the mass of an excited electron m(c)* > 146 GeV and on the QED cut-off parameters Lambda(+) > 149 GeV and Lambda(-) > 143 GeV. Upper limits are also set on the branching fractions of Z decaying into gamma gamma, pi degrees gamma and eta gamma of 5.2 x 10(-5), 5.2 x 10(-5) and 7.6 x 10(-5) respectively. The reactions e(+)e(-) --> rho(+)rho(-)n gamma (rho = e, mu, tau) are studied using the data collected from 1990 to 1994. The data are consistent with the QED expectations
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