The research activities of the Institute are focused on scientific areas and topics with direct or indirect social implications.
Ronzoni Institute has been building on its experience in synthesis and mechanism of action of biologically active substances. Most of the research is carried out in the laboratories of the Institute. The staff is assisted by fellows supported by public and private research grants. To extend the scope of its research, the Institute encourages collaborative work and the exchange of research workers with Italian and foreign laboratories and universities. Research reports are generally published in international specialized journals of chemistry, medicinal chemistry and biochemistry.
The Institute’s activities are mainly in experimental research, but also include educational activities and organization of meetings.
- Analytical profiling and chemo-physical properties.
- Structure and molecular conformation.
- Anticoagulant and antithrombotic heparin species
- Non-anticoagulant heparins as potential anticancer agents
- Non-anticoagulant heparins as potential anti-inflammatory
- Non-anticoagulant heparins as inhibitor of Hepcidin.
- Heparin Inhibits Cellular Invasion by SARS-CoV-2: Structural Dependence of the Interaction of the Spike S1 Receptor-Binding Domain with Heparin. Mycroft-West, C, Su, D, Pagani, I., Rudd, T.R., Elli, S., Guimond, S, Miller, Meneghetti, M.C.Z., Nader, H.B., LI, Y., Nunes, Q.M., Procter, P., Mancini, D., Clementi, M., Bisio, A., Forsyth, N.R., Ferro, V.,G, Turnbull, J., Guerrini, M., Fernig, D., Vicenzi, E., Yates, E.A., Lima, M., Skidmore M. Thromb Haemost. 120(12):1700-1715 (2020).
- BMP6 binding to heparin and heparan sulfate is mediated by N-terminal and C-terminal clustered basic residues. Denardo, A., Elli, S., Federici, S., Asperti, M., Gryzika M., Ruzzenenti, P., Carmona, F., Bergese, P., Naggi, A., Arosio, P., Poli, M. Biochim et Biophys Acta Gen Subj. 1865(2), 129799 (2020)
- Heparin-derived heparan sulfate mimics to modulate heparan sulfate-protein interaction in inflammation and cancer. Casu, B., Naggi, A., and Torri, G. Matrix Biol 29.6, 442-452 (2010)
- Generation of “neoheparin” from “E. Coli” K5 capsular polysaccharide. U. Lindahl, J.-P. Li, M. Kusche-Gullberg, M. Salmivirta, S. Alaranta, T. Veromaa, J. Emeis, I. Roberts, C. Trevor, P. Oreste, G. Zoppetti, A. Naggi, G. Torri, B. Casu. J. Med. Chem., 48, 349-352 (2005)
- Controversial glycosaminoglycan conformations. B. Casu, J. Choay, D. R. Ferro, G. Gatti, J.-C. Jacquinet, M. Petitou, A. Provasoli, M. Ragazzi, P. Sinaÿ, G. Torri. Nature, 322, 215-216, (1986)
- Chemometric analysis of heparin and crude heparin NMR spectra
- Combining NMR Spectroscopy and Chemometrics to Monitor Structural Features of Crude Heparin. Mauri, L., Marinozzi, M., Mazzini, G., Kolinski, R.E., Karfunkle, M., Keire, D.A., Guerrini, M. Molecules, 22 (7), 1146, (2017)
- Differentiation of generic enoxaparins marketed in the United States by employing NMR and multivariate analysis. Guerrini M, Rudd TR, Mauri L, Macchi E, Fareed J, Yates EA, Naggi A, Torri G. Anal Chem. 87(16), 8275-83. (2015)
- Unravelling structural information from complex mixtures utilizing correlation spectroscopy applied to HSQC spectra. Rudd T.R., Macchi E., Muzi L., Ferro M., Gaudesi D., Torri G., Casu B., Guerrini M., Yates E.A. Anal. Chem. 85, 7487-7493 (2013)
- Construction and use of a library of bona fide heparins employing 1H NMR and multivariate analysis. Rudd TR, Gaudesi D, Skidmore MA, Ferro M, Guerrini M, Mulloy B, Torri G, Yates EA. Analyst, 136,1380-1389 (2011).
Protein-carbohydrates interactions are the key events of many important pathophysiological processes. A deeper understanding of these interactions at the molecular level is critical for the development of novel effective therapeutics. Our research interests focus on the characterization of the 3D structure of carbohydrates and their molecular recognition by proteins and bio-macromolecules using complementary structural biology techniques, such as solution NMR, solid state NMR, Molecular Dynamics simulation, Zeta-potential, and Dynamic Light scattering.
- Grow Factors and Antithrombin binding oligosaccharides
- Interaction of heparin/LMWH with PF4
- Interaction of influenza A viral hemagglutinins with sialylated Glycans
- SARS-CoV2/sulfated polysaccharide interaction
- MD Simulation of the Interaction between Sialoglycans and the Second Sialic Acid Binding Site of Influenza A Virus N1 Neuraminidase. Elli, S., Gambacorta, N., Rudd, TR., Matrosovich, M., Guerrini, M. Biochem. J. in press (2021).
- Degeneracy of the Antithrombin Binding Sequence in Heparin: 2‐O‐Sulfated Iduronic Acid Can Replace the Critical Glucuronic Acid Elli S., Stancanelli E., Wang Z., Petitou M., Liu J., Guerrini M. Chem. Eur. J. 2020, 26, 11814 – 11818.
- Characterization of PF4-Heparin Complexes by Photon Correlation Spectroscopy and Zeta Potential. Bertini, S., Fareed, J., Madaschi, L., Risi, G., Torri, G., Naggi, A. Clin Appl Thromb Hemost, 23 (7), 725-734, (2017)
- Nuclear Magnetic Resonance and Molecular Dynamics Simulation of the Interaction between recognition Protein H7 of the Novel Influenza Virus H7N9 and Glycan Cell Surface Receptors. Macchi, E., Rudd, T. R., Raman, R., Sasisekharan, R., Yates, E. A., Naggi, A., Guerrini M., Elli, S. Biochemistry 55, 6605-6616, (2016).
- Antithrombin binding octasaccharides: role of extensions of the active pentasaccharide sequence on the specificity and strength of interaction. Evidence for very high affinity induced by an unusual glucuronic acid residue. Guerrini M., Guglieri, S., Casu, B., Torri, G., Mourier, P., Boudier, C. and Viskov, C. J. Biochem. Chem. 39, 26662-26675, (2008).
- Conformation of heparin pentasaccharide bound to antithrombin III. M. Hricovini, M. Guerrini, A. Bisio, G. Torri, M. Petitou, B. Casu. Biochemical J. 359II, 265- 272, (2001).
- Low molecular weight heparin
- Glycosaminoglycan mixtures
- Glatiramer acetate
- Pentosan polysulfate
- Conjugate extrogens
- Monoclonal antibody
- In-depth structural characterization of pentosan polysulfate sodium complex drug using orthogonal analytical tools. Alekseeva A, Raman R, Eisele G, Clark T, Fisher A, Lee SL, Jiang X, Torri G, Sasisekharan R, Bertini S. Carbohydr Polym. 15, 234, 115913, (2020).
- Fine structural characterization of sulodexide. Veraldi N, Guerrini M, Urso E, Risi G, Bertini S, Bensi D, Bisio A. J Pharm Biomed Anal. 15, 156, 67-79, (2018).
- Characterization of therapeutic protein AvidinOX by an integrated analytical approach. Giannini, G., Alekseeva, A., Naggi, A., Salvini, L., Tei, L., De Santis, R. Anal Bioanal Chem. 410 (2), 553-564 (2018).
- Characterization of danaparoid complex extractive drug by an orthogonal analytical approach. Gardini, C., Urso, E., Guerrini, M., Van Herpen, R., De Wit, P., Naggi, A. Molecules, 22 (7), art. no. 1116, (2017)
- Structural peculiarity and antithrombin binding region profile of mucosal bovine and porcine heparins. Naggi A, Gardini C, Pedrinola G, Mauri L, Urso E, Alekseeva A, Casu B, Cassinelli G, Guerrini M, Iacomini M, Baigorria V, Torri G. J Pharm Biomed Anal. 25,118, 52- 63 (2015).
The institute has given original contributions in chemistry of carbohydrate polymers, with special emphasis on chemical regioselective modification of polysaccharides as a strategy for deriving relationships between structure and properties.
The Institute gained expertise in high molecular weight polysaccharides, such as hyaluronic acid, chitosan, alginate, gellan gum, cellulose etc., typically used in pharmaceutical or food field. In particular, the group activity is focused mainly on functionalization and characterization of products by several chemical-physical techniques, such as solution and solid NMR, rheology and Light Scattering techniques. For example, the study of high viscosity/gel solutions containing hyaluronic acid is an important challenge to predict the biological activity of product in physiological conditions. This research activity has allowed to the design and set up different formulations in cosmetic, food and biomedical applications.
- Design and synthesis of chitosan-gelatin hybrid hydrogels for 3D printable in vitro models. Magli, S., Beatrice Rossi, G., Risi, G., Bertini, S., Cosentino, C., Crippa, L., Ballarini, E., Cavaletti, G., Piazza, L., Masseroni, E., Nicotra, F., Russo, L. Front. Chem., 14 July (2020)
- Novel N-acetyl-Glycol-split heparin biotin-conjugates endowed with anti-heparanase activity. Esposito, E., Vlodavsky, I., Barash, U., Roscilli, R., Milazzo, M.F., Giannini, G., Naggi, A. Eur J Med Chem 186 , 111831 (2020)
- Structural features of heparanase-inhibiting non-anticoagulant heparin derivative. Roneparstat. Alekseeva, A., Mazzini, G., Giannini, G., & Naggi, A. Carbohydr Polym, 156, 470-480, (2017)
- Lentinus edodesheterogalactan: Antinociceptive and anti-inflammatory effects E.R. Carbonero, A.H.P. Gracher, D.L. Komura, R. Marcon, C.S. Freitas, C.H. Baggio, A.R.S. Santos, G. Torri, P.A.J. Gorin, M. Iacomini. Food Chemistry 111 (2008) 531–537
- Solution studies of chitosan 6‐O‐sulfate. Terbojevich, M., Carraro, C., Cosani, A., Focher, B., Naggi, A. M., & Torri, G. (1989). Die Makromolekulare Chemie: Macromolecular Chemistry and Physics, 190(11), 2847-2855.
- Bacterial Nanocellulose and Its Surface Modification by Glycidyl Methacrylate and Ethylene Glycol Dimethacrylate. Incorporation of Vancomycin and Ciprofloxacin. Vismara, E., Bernardi, A., Bongio, C., Farè, S., Pappalardo, S., Serafini, A., … & Torri, G. (2019).Nanomaterials, 9(12), 1668.
The group has established experience in peptide synthesis, with emphasis on peptidomimetics of biological interest and study of their structure-activity relationship providing significant contribution to the synthesis of novel pseudo-amino acids and development of original methods for incorporation into peptides of extremely hindered building blocks.
In the last years, the group activity has focused to the synthesis of bioactive heparin/heparan sulphate oligosaccharides. The synthetic targets are currently aimed at synthesizing potential heparanase inhibitors. The research activities are conducted under the supervision of Dr M. Petitou, “father” of the synthetic heparin pentasaccharide, fondaparinux.
- Efficient selective deacetylation of complex oligosaccharides using the neutral organotin catalyst. Ni M, Guerrini M, Naggi A, Petitou M. Carbohydr Res. 498, 108172, (2020).
- Investigating glycol-split-heparin-derived inhibitors of heparanase: A study of synthetic trisaccharides. Ni, M., Elli, S., Naggi, A., Guerrini, M., Torri, G., Petitou, M. Molecules 21(11),1602 (2016).
- New macrocyclic analogs of the natural histone deacetylase inhibitor FK228; design, synthesis and preliminary biological evaluation. Ni M, Esposito E, Raj VP, Muzi L, Zunino F, Zuco V, Cominetti D, Penco S, Dal Pozzo A. Bioorg Med Chem. 23(21), 6785-93. (2015)
- New macrocyclic analogs of the natural histone deacetylase inhibitor FK228; design, synthesis and preliminary biological evaluation. Ni, M., Esposito, E., Raj, V. P., Muzi, L., Zunino, F., Zuco, V., Cominetti, D., Penco, S., Dal Pozzo, A. Bioorg Med Chem, 23(21), 6785-6793 (2015)
A number of polysaccharides of vegetal origin, like cellulose chitin, chitosan, and starch, are extensively studied polymers with established industrial applications. Among these, the starch-derived cyclodextrins are endowed with the unique property of forming inclusion complexes with a number of organic molecules whose size and shape fit into their macrocycles; such an inclusion can be exploited for protecting the guest molecules, modify their intrinsic solubility, and properly vectorize them. Advances in morphological and structural analysis of oligo- and polysaccharides and their derivatives permit a deeper insight into structural features important in determining their optimal application in various fields and to generate new products.
- cellulose derivatives
- synthetic polymers
- Enhanced polyhydroxyalkanoate (PHA) production from the organic fraction of municipal solid waste by using mixed microbial culture. Colombo, B., Favini, F., Scaglia, B., Sciarria, T.P., D’Imporzano, G., Pognani, M., Alekseeva, A., Eisele, G., Cosentino, C., Adani, F. Biotechnol Biofuels, 10 (1), art. no. 201 (2017).
- Hemp-based adsorbents for sequestration of metals: a review. Morin-Crini, N., Loiacono, S., Placet, V., Torri, G., Bradu, C., Kostić, M., … & Crini, G. (2019). Environmental Chemistry Letters, 17(1), 393-408.
- β-Chitin samples with similar microfibril arrangement change mechanical properties varying the degree of acetylation. Montroni, D., Fermani, S., Morellato, K., Torri, G., Naggi, A., Cristofolini, L. , Falini, G. Carbohydr Polym, 207, 26-33. (2019)
- Consequence of litter removal on pedogenesis: A case study in Bachs and Irchel (Switzerland). Scalenghe, R., Minoja, A.P., Zimmermann, S., Bertini, S. Geoderma, 271, 191-201, (2016)
- Inclusion complex characterization between progesterone and hydroxypropyl-β-cyclodextrin in aqueous solution by NMR study. Torri, G., Bertini, S., Giavana, T., Guerrini, M., Puppini, N., & Zoppetti, G. (2007). Journal of Inclusion Phenomena and Macrocyclic Chemistry, 57(1-4), 317-321.
- Cyclodextrins, from molecules to applications. Crini, G., Fourmentin, S., Fenyvesi, É., Torri, G., Fourmentin, M., & Morin-Crini, N. (2018). Environmental chemistry letters, 16(4), 1361-1375.
- Alpha cellulose from industrial and agricultural renewable sources like short flax fibres, ears of corn and wheat-straw and its transformation into cellulose acetates. Vismara, E., Gastaldi, G., Valerio, A., Bertini, S., Cosentino, C., & Eisle, G. (2009). Journal of Materials Chemistry, 19(45), 8678-8686.
The Institute contributed to the first applications of nuclear magnetic resonance (NMR) spectroscopy to carbohydrates and their polymers and is currently engaged on several fronts with various international organizations to verify the equivalence of generic / biosimilar drugs through analytical methodologies to avant-garde and proprietary, operating in quality.
On behalf of MIT and the Food and Drug Administration (FDA), he made an essential and rapid contribution to the solution of the “heparin crisis” that had caused over one hundred deaths in the United States by identifying the responsible contaminant presence.
- 1D and 2D-HSQC NMR: Two Methods to Distinguish and Characterize Heparin From Different Animal and Tissue Sources. Mauri L, Marinozzi M, Phatak N, Karfunkle M, St Ange K, Guerrini M, Keire DA, Linhardt RJ. Front Med (Lausanne). 27;6:142. (2019)
- Heparanase as an additional tool for detecting structural peculiarities of heparin oligosaccharides. Alekseeva, A., Urso, E., Mazzini, G., & Naggi, A. Molecules, 24(23), 4403, (2019)
- Molecular Weights of Bovine and Porcine Heparin Samples: Comparison of Chromatographic Methods and Results of a Collaborative Survey. Bertini, S., Risi, G., Guerrini, M., Carrick, K., Szajek, A.Y., Mulloy, B. Molecules, 22 (7), (2017).
- Qualification of HSQC methods for quantitative composition of heparin and low molecular weight heparins Mauri, L., Boccardi, G., Torri, G., Karfunkle M., Macchi, E., Muzi, L., Keire, D., Guerrini, M. J Pharm Biomed Anal 136, p. 92-105 (2017)
- Structural characterization of the low-molecular-weight heparin dalteparin by combining different analytical strategies. Bisio, A., Urso, E., Guerrini, M., De Wit, P., Torri, G., Naggi, A. Molecules, 22(7), 1051 (2017)
- Oversulfated chondroitin sulfate is a contaminant in heparin associated with adverse clinical events. Guerrini M, Beccati D, Shriver Z, Naggi A, Viswanathan K, Bisio A, Capila I, Lansing JC, Guglieri S, Fraser B, Al-Hakim A, Gunay NS, Zhang Z, Robinson L, Buhse L, Nasr M, Woodcock J, Langer R, Venkataraman G, Linhardt RJ, Casu B, Torri G, Sasisekharan R. Nat Biotechnol. 26: 669-675 (2008).
- Cellulose and derivatives
- Chitin and chitosan
- Synthetic polymers
- Cross-linked cyclodextrin-based material for treatment of metals and organic substances present in industrial discharge waters. Euvrard, É., Morin-Crini, N.Druart, C. Bugnet, J. Martel, B. Cosentino, C. Moutarlier, V. Crini, G. Beilstein. J Org Chem 12, 1826–1838 (2016).
- Hydration of calcium sulphoaluminate clinker with additions of different calcium sulphate sources Allevi S, Marchi M, Scotti F, Bertini S, Cosentino C. Materials and Structures 49(1-2), 453-466 (2016)
- Studying soil organic matter using 13C CP-MAS NMR: the effect of soil chemical pre-treatments on spectra quality and representativity. S. Salati, F. Adani, C. Cosentino, G. Torri. Chemosphere, 70, 2092-2098 (2008)
- Structural differences between chitin polymorphs and their precipitates from solutions—evidence from CP-MAS 13C-NMR, FT-IR and FT-Raman spectroscopy. Focher, B., Naggi, A., Torri, G., Cosani, A., & Terbojevich, M. Carbohydr Polym, 17(2), 97-102 (1992)
- Structural differences between non-wood plant celluloses: evidence from solid state NMR, vibrational spectroscopy and X-ray diffractometry. B. Focher, M. T. Palma, M. Canetti, G. Torri, C. Cosentino, G. Gastaldi. Ind. Crops Products 13:193-208 (2001)
- Characterization of Nimesulide/β-cyclodextrin composite obtained by solid state activation. Magarotto, L., Bertini, S., Cosentino, C., & Torri, G. (2001).In Journal of Metastable and Nanocrystalline Materials (Vol. 10, pp. 643-648). Trans Tech Publications Ltd.