11,916 research outputs found
La religion, la liberté, la justice. Un commentaire des Lettres écrites de la Montagne
No full textL’uso del drone nella documentazione archeologica: il castello di Montefalco in Sabina (RM)
No full textBernardi, M., Fasson, F. (2022). L’uso del drone nella documentazione archeologica: il castello di Montefalco in Sabina (RM). GEOMEDIA, XXVI(2), 34-36
Il Sessantotto, e poi?
No full textWorkshop di Studi suddiviso in tre sezioni: "Il Sessantotto politico", con interventi di Paola Bernasconi e Loredana Guerrieri e Alberto De Bernardi; "La circolazione delle idee del Sessantotto", con interventi di Antonio Benci e Aysen Uysal e Andrea Rapini, "Il Sessantotto culturale e mediatico", con interventi di Silvia Casilio, Gianpaolo Fissore e Audrey Leblanc e Giacomo Manzoli. A conclusione dei lavori una tavola rotonda a cui hanno partecipato A. De Bernardi, R. Guillot, G. Manzoli, A. Rapini, V. Romitelli, F. Rossi, M. Tolomelli
Glycomimetic antagonists of the C-lectin DC-SIGN
No full textDC-SIGN (Dendritic Cell-Specific Intercellular adhesion molecule 3-Grabbing Nonintegrin), a specific C-type lectin recognizing pathogen-cell surface glycoproteins, is a trans-membrane receptor on immature dendritic cells (DC) which binds a number of pathogen-associated molecular patterns. Normally, this binding event triggers internalization of the DC-SIGN-pathogen complex followed by lysosomal degradation of the pathogen and conjugation of the resulting fragments with MHC-II to initiate an adaptive immune response from T cells. Some pathogens, however, have been reported to take advantage of this mechanism, as they appear to deter DC maturation through DC-SIGN-mediated signalling and inhibit antigen presentation to T cells. In particular, van Kooyk’s group has shown that HIV-1 enters DC via DC-SIGN avoiding lytic degradation [1]. By doing so, HIV-1 not only escapes the host immune system, but also is presented directly to T cells, which enables fully disseminated HIV-1 infection.
Inhibition of pathogen interaction using DC-SIGN specific antagonists is considered as a plausible concept for the development of novel anti-infective agents. Several groups have recently demonstrated that inhibition of DC-SIGN, either by designed glycoconjugates or by antibodies, prevents pathogen attachment to DC and inhibits the infection of other immune cells at its earliest steps [2].
Our group has been active in this area and, in collaboration with the European network Carmusys [3] has developed mannose-based and fucose-based glycomimetic ligands that inhibit DC-SIGN mediated HIV infection in cellular and tissue models [4].
The presentation will deal with the design and synthesis of the glycomimetic monovalent ligands, the process of structural optimization which allowed us to build affinity and selectivity in their structure, the synthesis and optimization of polyvalent constructs that allowed us to achieve high affinity interaction with the lectin.
[1] van Kooyk, Y. ; Geijtenbeek, T.B.H. Nat Rev Immunol, 3, 2003, 697.
[2] For reviews, see: (a) Ernst, B. ; Magnani J.L. Nat Rev Drug Discov 8, 2009, 661 and references therein; (b) Anderluh, M., et al. Curr Med Chem, 2012, 19, 992 and references therein.
[4] http://www.carmusys.iiq.csic.es/
[5] (a) Berzi, A.; Reina, J. J.; Ottria, R.; Sutkeviciute, I.; Antonazzo, P.; Sanchez-Navarro, M.; Chabrol, E.; Biasin, M.; Trabattoni, D.; Cetin, I.; Rojo, J.; Fieschi, F.; Bernardi, A.; Clerici, M. Aids 2012, 26, 127-37; (b) Obermajer, N.; Sattin, S.; Colombo, C.; Bruno, M.; Svajger, U.; Anderluh, M.; Bernardi, A. Mol Divers 2011, 15, 347-360; (c) Luczkowiak, J.; Sattin, S.; Sutkeviciute, I.; Juan Reina, J.; Sanchez-Navarro, M.; Thepaut, M.; Martinez-Prats, L.; Daghetti, A.; Fieschi, F.; Delgado, R.; Bernardi, A.; Rojo, J. Bioconjugate Chem 2011, 22, 1354-1365; (d) Guzzi, C.; Angulo, J.; Doro, F.; Reina, J. J.; Thepaut, M.; Fieschi, F.; Bernardi, A.; Rojo, J.; Nieto, P. M. Org Biomol Chem 2011, 9, 7705-7712; (e) Andreini, M.; Doknic, D.; Sutkeviciute, I.; Reina, J. J.; Duan, J.; Chabrol, E.; Thepaut, M.; Moroni, E.; Doro, F.; Belvisi, L.; Weiser, J.; Rojo, J.; Fieschi, F.; Bernardi, A. Org Biomol Chem 2011, 9, 5778-5786; (f) Sattin, S.; Daghetti, A.; Thepaut, M.; Berzi, A.; Sanchez-Navarro, M.; Tabarani, G.; Rojo, J.; Fieschi, F.; Clerici, M.; Bernardi, A. Acs Chem Biol 2010, 5, 301-31
Glycomimetic antagonists of mannose-specific C-lectins
No full textOver the past few years our group has been designing and synthesizing glycomimetic molecules capable of antagonizing mannose-specific C-lectins. They were designed taking advantage of the 3D structure of known oligosaccharide ligands and of available structural information on the lectin/ligand complexes. The small-molecule monovalent ligands obtained are often endowed with limited protein affinity, but display improved drug-like properties compared to natural sugars.
This approach has allowed to identify promising mimetic leads which are giving encouraging results as antagonists of the dendritic cell lectin DC-SIGN1 and of the soluble Mannose Binding Lectin (MBL),2 recently implicated in reperfusion damage following brain stroke events. Multivalent presentation on polymeric scaffolds of these ligands has afforded high-affinity antagonists, and the selectivity of these materials against different C-lectins is being investigated.
Updates of our research will be discussed in the presentation.
[1] (a) N. Varga, I. Sutkeviciute, C. Guzzi, J. McGeagh, I. Petit-Haertlein, S. Gugliotta, J. Weiser, J. Angulo, F. Fieschi, A. Bernardi Chem. Eur. J. 2013, 19, 4786 – 4797; (b) M. Thépaut, C. Guzzi, I. Sutkeviciute, S. Sattin, R. Ribeiro-Viana, N.t Varga, E. Chabrol, J. Rojo, J. Angulo, A. Bernardi, P. M. Nieto, F. Fieschi J. Am. Chem. Soc. 2013, 135, 2518–2529
[2] F. Orsini, P. Villa, S. Parrella, R. Zangari, E. R. Zanier, R. Gesuete, M. Stravalaci, S. Fumagalli, R. Ottria, J. J. Reina, A. Paladini, E. Micotti, R. Ribeiro-Viana, J. Rojo, V. I. Pavlov, G. L. Stahl, A. Bernardi, M. Gobbi, M.G. De Simoni Circulation 2012, 126, 1484-149
Industrial Relevance of Asymmetric Organocatalysis in the Preparation of Chiral Amine Derivatives in Methodologies in Amine Synthesis (Eds.: A. Ricci, L. Bernardi)
No full textThis chapter covers the emerging utilization of organocatalytic methodologies in industrial settings directed at the large-scale preparation of enantioenriched amines and N-heterocycles. First, some selected manufacturing processes, based on organocatalytic stereodetermining steps, are commented concisely. Despite the generally high catalyst loadings required, these examples show that the relatively low cost of organic catalysts makes the development of cost-effective industrial routes possible. Then, three case studies (pregabalin, the bicyclic core of telaprevir, and 5-(trifluoromethyl)-2-isoxazolines) are discussed. These chiral targets have been approached through a variety of enantioselective strategies, among which the organocatalytic ones stand out for their versatility and potential for scale-up. Recent applications of organocatalysis in industrial settings are not restricted to a single activation mode or a class of catalysts. They encompass the whole catalyst and reaction repertoire typical of this relatively novel catalytic approach to asymmetric synthesis. Asymmetric organocatalysis proves to be, therefore, a useful and versatile synthetic tool for the industrial preparation of chiral compounds
Industrial Relevance of Asymmetric Organocatalysis in the Preparation of Chiral Amine Derivatives in Methodologies in Amine Synthesis (Eds.: A. Ricci, L. Bernardi)
No full textProvides a unique overview of efficient synthetic routes to one of the most important compound classes in organic and pharmaceutical chemistry!
Amines are among the most important compounds in organic chemistry due to their wide occurrence in natural products, drugs, crop protection compounds, and advanced materials. For example, the majority of drugs are amines or contain functional groups derived from amines. Powerful and efficient methods for the introduction of the amino group are therefore of great importance to synthetic chemists in academia and industry.
Methodologies in Amine Synthesis ? Challenges and Applications presents powerful and state-of-the-art methods for the efficient preparation of amines. It summarizes recent advances in the electrophilic amination reaction, hydroamination, C?H amination as well as newly developed photocatalytic approaches. It further describes organocatalytic and enzymatic routes to the generation of amines under mild and environmentally friendly conditions. In addition, it highlights the relevance of the amino function in bioactive molecules, drugs, and in the engineering of smart materials. Finally, the application of palladium-catalyzed aromatic amination in industrial context is critically discussed.
* Only up-to-date and comprehensive book on the preparation of amines ? one of the most frequently occurring compound classes found in natural products, bioactive molecules, and advanced materials.
* Presents efficient and useful synthetic methods, highlights opportunities/ challenges as well as applications in pharmaceutical chemistry and materials science.
* Chapters are compiled by well-known experts in the field. One of them edited the previous books ?Modern Amination Methods? (2001) and ?Amino Group Chemistry? (2007).
The book Methodologies in Amine Synthesis ? Challenges and Applications is a musthave for chemists in academia and industry working in the field of organic synthesis and catalysis, natural product chemistry, drug synthesis and pharmaceutical chemistry, as well as materials science
Possession et théâtre
No full textUna presentazione di diversi modelli energetici in funzione di una teoria del performer. Include anche un resoconto sintetico dei risultati di una pluriennale ricerca sul campo in Europa e in Asia. Durante il suo intervento, Vito Di Bernardi ha ampliato il testo poi pubblicato con numerose esemplificazioni tratte dalla sua ricerca sul teatro dell'isola di Bali
Benzofuran Derivatives Activators of the Chaperone Protein Hsp90: Synthesis, Interaction Studies and Biological Effects
No full textWe have recently reported that allosteric modulation of the chaperone protein Hsp901 can be achieved in an allosteric fashion using a family of 2-phenyl-benzofuran derivatives that target an allosteric pocket at the C-terminal domain of the protein.2,3 These ligands are mainly activators of the chaperone ATPase activity3 and are accelerators of the protein internal dynamics.4 As a result, they tune Hsp90 chaperone activity in ways that we are just beginning to unravel.
We are going to present the synthetic approaches towards an expanded library of about 40 benzofuran derivatives diversified at positions R1 and R2 along with the interaction studies with full length Hsp905 and the effects on Hsp90 enzymatic and chaperoning activity.
Figure 1: 2-phenyl-benzofuran diversification at positions R1 and R2 (top) and docked complex of Hsc82 (Hsp90 yeast form) with one of our derivatives (bottom).
1. Jackson, S. E. In Molecular Chaperones; Jackson, S., Ed.; Springer Berlin Heidelberg: 2013; Vol. 328, p 155.
2. Morelli, L.; Bernardi, A.; Sattin, S. Carbohydr Res 2014, 390C, 33.
3. Sattin, S.; Tao, J.; Vettoretti, G.; Moroni, E.; Pennati, M.; Lopergolo, A.; Morelli, L.; Bugatti, A.; Zuehlke, A.; Moses, M.; Prince, T.; Kijima, T.; Beebe, K.; Rusnati, M.; Neckers, L.; Zaffaroni, N.; Agard, D. A.; Bernardi, A.; Colombo, G. Chem. Eur. J. 2015, 21, 13598.
4. Vettoretti, G.; Moroni, E.; Sattin, S.; Tao, J.; Agard, D. A.; Bernardi, A.; Colombo, G. Sci Rep 2016, 6, 23830.
5. Sattin, S.; Panza, M.; Vasile, F.; Berni, F.; Goti, G.; Tao, J.; Moroni, E.; Agard, D.; Colombo, G.; Bernardi, A. Eur. J. Org. Chem. 2016, DOI: 10.1002/ejoc.201600420
Influence of allosteric Hsp90 ATPase activators on its chaperoning activity
No full textHsp90 is a molecular chaperone with a starring role in the cell life cycle1 and an established anti-apoptotic target in cancer therapy.2 The protein internal dynamics are regulated by ATP and are critical for its function. Hsp90 can be modulated in an allosteric fashion as we have recently demonstrated, targeting the protein C-terminal domain (CTD) with a family of 2-phenyl-benzofuran derivatives.3-5 These compounds accelerate Hsp90 internal dynamics and increase its enzymatic ATPase activity. As a result, they tune its chaperone activity in ways that we are just beginning to unravel.
The synthetic approaches towards an expanded library of about 40 benzofuran derivatives will be presented. The interaction studies with full length Hsp90,6 and the effects on Hsp90 enzymatic and chaperoning activity will be reported for selected compounds.
References
1. S. E. Jackson In Molecular Chaperones; Jackson, S., Ed.; Springer Berlin Heidelberg (2013) Vol. 328, p 155-240.
2. J. Trepel, M. Mollapour, G. Giaccone, and L. Neckers Nat Rev Cancer (2010), 10, 537-549.
3. L. Morelli, A. Bernardi and S. Sattin, Carbohydr. Res. (2014), 390, 33-41.
4. S. Sattin et al Chem. Eur. J. (2015), 21, 13598-13608.
5. G. Vettoretti, E. Moroni, S. Sattin, J. Tao, D.A. Agard, A. Bernardi and G. Colombo Sci Rep (2016), 6, 23830.
6. S. Sattin, M. Panza, F. Vasile, F. Berni, G. Goti, J. Tao, E. Moroni, D.A. Agard, G. Colombo and A. Bernardi
Eur. J.Org. Chem. (2016) DOI: 10.1002/ejoc.201600420
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