1,725,907 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
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
Robert Bertucci
No full textA portrait photograph of Robert A. Bertucci. he is wearing a white, button down Temple University shirt.Robert A. Bertucci is a graduate of Springfield College in 1974. While at Springfield College, he served as captain for the men's volleyball team and participated in the team's first ever Division I final four appearance in 1971. Bertucci went on to become a highly decorated and celebrated collegiate volleyball coach. He coached at Rutgers University (1987-1993), Temple University (1995-2010), and Lehigh (2011- ), as well as working for USA Volleyball and serving as member of the US Women's National Team. He has been inducted into the YMCA Volleyball Hall of Fame (2008) and the Springfield College Athletic Hall of Fame (2017).This image was donated to the Archives from the SC Athletic Department. It was donated as a electronic file. The photograph was printed out and a physical copy was placed into the Student File. The original copy of this photographic print does not currently exist in the Archives
Robert Bertucci deep in thought
No full textA photograph of Robert A. Bertucci deep in thought on the sidelines during a Volleyball match. Bertucci is seated and has chin resting on his right hand in a thoughtful pose. He is looking out at the court. In the distance two volleyball players are standing and also watching the match.Robert A. Bertucci is a graduate of Springfield College in 1974. While at Springfield College, he served as captain for the men's volleyball team and participated in the team's first ever Division I final four appearance in 1971. Bertucci went on to become a highly decorated and celebrated collegiate volleyball coach. He coached at Rutgers University (1987-1993), Temple University (1995-2010), and Lehigh (2011- ), as well as working for USA Volleyball and serving as member of the US Women's National Team. He has been inducted into the YMCA Volleyball Hall of Fame (2008) and the Springfield College Athletic Hall of Fame (2017).This image was donated to the Archives from the SC Athletic Department. It was donated as a electronic file. The photograph was printed out and a physical copy was placed into the Student File. The original copy of this photographic print does not currently exist in the Archives
Robert Bertucci pacing sidelines
No full textA photograph of Robert Bertucci pacing the sidelines during a Volleyball match of the Temple University Volleyball Team. Bertucci is wearing a Red Temple shirt and has a folder raised up close to his face in his right hand. He seems to be walking briskly toward the court. Spectators are seen behind him in the bleachers.Robert A. Bertucci is a graduate of Springfield College in 1974. While at Springfield College, he served as captain for the men's volleyball team and participated in the team's first ever Division I final four appearance in 1971. Bertucci went on to become a highly decorated and celebrated collegiate volleyball coach. He coached at Rutgers University (1987-1993), Temple University (1995-2010), and Lehigh (2011- ), as well as working for USA Volleyball and serving as member of the US Women's National Team. He has been inducted into the YMCA Volleyball Hall of Fame (2008) and the Springfield College Athletic Hall of Fame (2017).This image was donated to the Archives from the SC Athletic Department. It was donated as a electronic file. The photograph was printed out and a physical copy was placed into the Student File. The original copy of this photographic print does not currently exist in the Archives
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
Robert A. Bertucci and Yun Yi Zhang
No full textA photograph of Robert A. Bertucci and Yun Yi Zhang sitting on a bench during a Volleyball match of the Temple University Women's Volleyball team. Yun Yi is looking at Bertucci as he is explaining something to her. Bertucci is leaning back and gesturing with his left hand. There are spectators in the background.Robert A. Bertucci is a graduate of Springfield College in 1974. While at Springfield College, he served as captain for the men's volleyball team and participated in the team's first ever Division I final four appearance in 1971. Bertucci went on to become a highly decorated and celebrated collegiate volleyball coach. He coached at Rutgers University (1987-1993), Temple University (1995-2010), and Lehigh (2011- ), as well as working for USA Volleyball and serving as member of the US Women's National Team. He has been inducted into the YMCA Volleyball Hall of Fame (2008) and the Springfield College Athletic Hall of Fame (2017).This image was donated to the Archives from the SC Athletic Department. It was donated as a electronic file. The photograph was printed out and a physical copy was placed into the Student File. The original copy of this photographic print does not currently exist in the Archives
Robert Bertucci coaching
No full textA photograph of Robert Bertucci on the sideline coaching the Temple University Volleyball team during a volleyball game. He is wearing a Temple University seat. Specatators can be seen in seats behind him. In the foreground stands a volleyball player, but you just see her back in the photograph.Robert A. Bertucci is a graduate of Springfield College in 1974. While at Springfield College, he served as captain for the men's volleyball team and participated in the team's first ever Division I final four appearance in 1971. Bertucci went on to become a highly decorated and celebrated collegiate volleyball coach. He coached at Rutgers University (1987-1993), Temple University (1995-2010), and Lehigh (2011- ), as well as working for USA Volleyball and serving as member of the US Women's National Team. He has been inducted into the YMCA Volleyball Hall of Fame (2008) and the Springfield College Athletic Hall of Fame (2017).This image was donated to the Archives from the SC Athletic Department. It was donated as a electronic file. The photograph was printed out and a physical copy was placed into the Student File. The original copy of this photographic print does not currently exist in the Archives
Robert Bertucci pacing the sidelines
No full textA photograph of Robert A. Bertucci pacing the sidelines during a Volleyball match when he coached at Temple University. Bertucci is wearing a white Temple shirt and black pants. His hands are by his side and he is looking toward the court. Behind are spectators seating in the bleachers.Robert A. Bertucci is a graduate of Springfield College in 1974. While at Springfield College, he served as captain for the men's volleyball team and participated in the team's first ever Division I final four appearance in 1971. Bertucci went on to become a highly decorated and celebrated collegiate volleyball coach. He coached at Rutgers University (1987-1993), Temple University (1995-2010), and Lehigh (2011- ), as well as working for USA Volleyball and serving as member of the US Women's National Team. He has been inducted into the YMCA Volleyball Hall of Fame (2008) and the Springfield College Athletic Hall of Fame (2017).This image was donated to the Archives from the SC Athletic Department. It was donated as a electronic file. The photograph was printed out and a physical copy was placed into the Student File. The original copy of this photographic print does not currently exist in the Archives
Induced circular dichroism of drug-albumin complexes: characterization of binding modes by quantum chemical calculations
No full textThe stereospecificity of high-affinity biorecognition phenomena at the basis of the activity of drugs is an important topic of active research in medicinal chemistry, contributing to the design and development of new potent and
selective drugs. The binding of drugs to their targets may lead to the onset of an induced circular dichroism (ICD)
signal, which can be detected experimentally (Figure 1). ICD spectroscopy, therefore, provides versatile and useful methods for characterizing the structural and dynamic properties of the binding of drugs to target proteins. [1]
Within this framework, the combined application of experimental ICD spectroscopy and quantum chemical (QC)
calculations based on density functional theory (DFT) and its time-dependent formulation (TD-DFT) is a recently
emerging approach which allows to identify the conformational features of ligands bound to target proteins even
in the absence of a detailed structure of the binding sites, either obtained from experimental X-ray crystallography
and NMR measurements or from computational models of the complex. [2] QC methods can be used to determine
the theoretical chiroptical responses of all the possible conformations of drugs bound to their hosts and compare
them with the experimental ICD spectra of drug–host complexes. For instance, the peculiar species-dependent
ICD spectra observed for the binding of (S)-ketoprofen to different serum albumins could be explained by the selection of different mutual arrangements of the phenyl moieties inside the binding pocket, contributing to a better
understanding of the changes in the pharmacokinetic and pharmacodynamic profiles of drugs among different
species. [3] Further applications of this combined ICD/QC approach to the characterization of the binding modes
of known ligands for the high-affinity binding sites of human serum albumin (HSA) will be reported, namely for
pyrazolidine-3,5-diones and benzodiazepines, which are frequently used as ICD binding markers for Sudlow’s
site I and site II, respectively. [1]
1. Tedesco, D.; Bertucci, C. Induced circular dichroism as a tool to investigate the binding of drugs to carrier proteins: Classic approaches and new trends. J. Pharm.
Biomed. Anal. 2015, in press, doi: 10.1016/j.jpba.2015.02.024.
2. Ionescu, S.; Matei, I.; Tablet, C.; Hillebrand, M. Theoretical ECD calculations – a useful tool for estimating the conformational change of a ligand in the binding
pocket of proteins. Phys. Chem. Chem. Phys. 2013, 15, 11604-14.
3. Tedesco, D.; Pistolozzi, M.; Zanasi, R.; Bertucci, C. Characterization of the species-dependent ketoprofen/albumin binding modes by induced CD spectroscopy and
TD-DFT calculations. J. Pharm. Biomed. Anal. 2015, in press, doi: 10.1016/j.jpba.2014.11.029
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