1,357,931 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 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
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 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
Conformational flexibility and absolute stereochemistry of (3R)-3-hydroxy-4-aryl-β-lactams investigated by chiroptical spectroscopies and TD-DFT calculations
No full textβ-lactam rings play a key role in medicinal chemistry: β-lactam derivatives are widely used
in therapy as antibiotics, cholesterol absorption and prostate-specific antigen inhibitors.
Stereochemical characterisation is crucial for the application of β-lactam rings as chiral
intermediates for the asymmetric synthesis of a variety of compounds of medicinal interest,
such as proteinogenic and non-proteinogenic amino acids and taxanes. [1]
The absolute stereochemistry of a series of synthetic (3R)-3-hydroxy-4-aryl-β-lactams
was investigated by means of chiroptical spectroscopies, i.e. polarimetry and electronic
circular dichroism (ECD), and quantum mechanical (QM) calculations using time-
dependent density functional theory (TD-DFT). The absolute configuration at C3 was
assigned by chemical correlation with synthetic precursors; the overall stereochemistry was
assessed by application of the β-lactam sector rule, which relates the sign of the specific
rotatory power ([α] D ) and the lowest-energy ECD band with the absolute configuration at
C4. [1] The assessed absolute configurations were then confirmed by TD-DFT calculations.
The β-lactam sector rule allowed a correct stereochemical
characterisation of the investigated β-lactams, with the exception of a
thienyl-substituted derivative (1). Conformationally-averaged TD-DFT
calculations yielded accurate predictions of ECD spectra in 2-propanol
and [α] D values in chloroform, which allowed to assign the correct
absolute configuration to compound 1. [α] D values in acetone were
successfully predicted by TD-DFT calculations with explicit treatment
of solvent molecules at a QM level. [2]
A detailed analysis of the geometric features of the β-lactam ring for all the equilibrium
conformers, as obtained by DFT geometry optimisation, helped to identify regular patterns
for the arrangement of atoms around the carbonyl chromophore, which is responsible for
the chiroptical properties of β-lactam derivatives. This study showed the importance of
conformational flexibility for the definition of chiroptical properties, and highlighted
strengths and weaknesses of the different methods for the stereochemical characterisation
of chiral molecules in solution.
References
[1] Barbaro, G., Battaglia, A., Guerrini, A., Bertucci, C., Geremia, S., Tetrahedron:
Asymmetry 9 (1998), 3401-3409.
[2] Tomasi, J., Mennucci, B., Cammi, R., Chem. Rev. 105 (2005), 2999-3093
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
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