Our Research

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.

Heparin and heparan sulfate are linear, sulfated, polydisperse polysaccharide of animal origin belonging to the class of glycosaminoglycans (GAGs). Heparin and low-molecular weight heparins (LMWHs) are widely used in the anticoagulant and antithrombotic therapy. LMWHs and non-anticoagulant heparin derivatives are also promising candidate drugs against cancer and inflammation. Though deceptively simple, the structure of heparin and other GAGs is complex. Unravelling features associated with its different biological activities with the eventual aim of dissecting them and generating more potent and more specific drugs requires convergent use of chemical and enzymatic cleavage and advanced NMR and LC-MS methods. Systematic chemical and/or enzymatic modification of heparin and related GAGs is a valuable strategy for structure-activity studies as well as for obtaining novel molecules endowed with better binding properties towards proteins associated with different biological activitie
  • 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.
selected publications
Chemometric techniques, particularly multivariate analysis methodologies (PCA), have long been used in the analysis of complex datasets, such as for example the metabolic profiles obtained through chromatographic and / or spectroscopic methods. The application of these approaches to one-and two-dimensional NMR spectra can be used to detect unknown contaminants as well as to differentiate the heparin and heparin-derivatives on the basis of their structural features and animal/organ of origin.  Ronzoni has libraries of spectra of validated “bona fide” heparin and heparin-derivatives samples defining the current statistical definition of each class of product.
  • Chemometric analysis of heparin and crude heparin NMR spectra
selected publications

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
selected publications
The number of complex drug substances, including biologics, present in the different pharmacopoeias has increased in the last decades. These drugs are distinct from chemically synthetized pharmaceutical products, since they do not represent a single entity, but a complex combination of substances or heterogeneous substances. They are usually, extracted from natural sources such as human, animal, vegetal, microorganisms, prepared chemically or produced by biotechnological methods. Our research is aimed at the development of orthogonal analytical approaches to assess the structural features of these drugs, particularly LC-MS and NMR techniques.
  • Low molecular weight heparin
  • Glycosaminoglycan mixtures
  • Glatiramer acetate
  • Pentosan polysulfate
  • Conjugate extrogens
  • Monoclonal antibody
  • Defibrotide
selected publications

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.

selected publications

 

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.  

selected publications

 

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
  • cyclodextrin
  • synthetic polymers
  • polyhydroxyalkanoate

selected publications

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.

 

selected publications

CP-MAS NMR spectroscopy (Cross Polarization Magic Angle Spinning) is an important means of investigation for the study of materials in general. Solid state NMR spectroscopy is a non-destructive technique and independent of the solubility of the samples under examination and lends itself to the characterization of polysaccharides such as cellulose, starch, chitin. Through measurement of the relaxation and polarization transfer times (T1 rho and TCH), morphological properties and homogeneity of the systems can be investigated like the interaction between the different organic and inorganic components.
  • Cellulose and derivatives
  • Starch
  • Chitin and chitosan
  • Synthetic polymers
selected publications

Istituto di Ricerche Chimiche e Biochimiche G. Ronzoni – Fondazione non profit – Via G. Colombo 81 – 20133 MILANO – igr-ronzoni@legalmail.it – C.F. 01110900154